Effects of acupuncture on brain functional networks in patients with mild cognitive impairment and Alzheimer’s disease: a systematic review and activation likelihood estimation meta-analysis of neuroimaging studies

Introduction

Alzheimer’s disease (AD), previously recognized as senile dementia, is a progressive neurodegenerative disorder predominantly affecting older adults, although early-onset cases have also been documented (1,2). As the primary cause of dementia, AD affects about 5.6% of Chinese individuals aged 65 years and older, with prevalence climbing to 20% among those over 85 years old (3,4). This trend will likely be exacerbated, with global aging causing a sharp rise in incidence, placing a substantial burden on healthcare systems and societies worldwide. AP manifests through a gradual erosion of cognitive functions—memory, thinking, judgment, language, and executive abilities—ultimately reducing individuals’ autonomy (5). Meanwhile, mild cognitive impairment (MCI) is a critical transitional stage between normal aging and dementia, often preceding AD. It is characterized by more pronounced memory or cognitive decline than that typical for a given age and does not significantly disrupt daily life. A recent study estimated that the prevalence of MCI is 15.5% among Chinese adults (6), and a 2021 study on East China found a prevalence of 12.2% among those aged 55 years and older and 17% among those older than 60 years (7), rising sharply to 42% among those older than 85 years. Overall, MCI is a pivotal precursor in the continuum of neurodegenerative disease (8,9).

Acupuncture, a key element of traditional Chinese medicine (TCM), has been proposed as a potential therapy for AD and MCI. Research has indicated its ability to improve cognitive function, regulate neurotransmitters, reduce pathological changes, and facilitate a multifaceted treatment approach, while also supporting health maintenance and disease prevention (10). Resting-state functional magnetic resonance imaging (rs-fMRI), a robust neuroimaging method, measures spontaneous brain activity via blood oxygen level-dependent (BOLD) signals (11). It reveals functional connectivity within neural networks, such as the default mode network (DMN), which is disrupted in individuals’ neurodegenerative diseases (12,13). Thus, rs-fMRI may be used to effectively clarify the therapeutic mechanisms underlying acupuncture’s effect in AD and MCI. Lin et al. used rs-fMRI and reported enhanced functional connectivity in cognition-related brain regions, such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex, following acupuncture at specific points, including Yintang (EX-HN3), Neiguan (PC6), Taixi (KI3), Fenglong (ST40), and Taichong (LR3) (14). Acupuncture, a cornerstone of TCM, is used to modulate physiological and neurological functions, offering therapeutic benefits for patients with AD and MCI. In TCM, acupuncture points are selected to regulate the flow of qi (vital energy) and restore balance, which can support cognitive and emotional health. For clarity, we describe the key acupuncture points below, outlining their significance in TCM with reference to the related anatomical locations and clinical applications (15).

The Hegu point (LI4), located on the dorsum of the hand between the first and second metacarpal bones at the midpoint of the radial side of the second metacarpal, is commonly used in TCM to promote mental clarity, alleviate stagnation, and regulate qi. When paired with Taichong (LR3), it is believed to calm the mind, reduce neurological overstimulation (referred to as extinguishing wind in TCM), and address symptoms such as spasms. The acupuncture technique for Hegu involves a 0.5- to 1-inch perpendicular needle insertion coupled with balanced supplementation and drainage methods, with the needle retained for 8 minutes after deqi (a sensation indicating effective needle stimulation) is achieved (16).

The Taichong point (LR3), situated on the dorsum of the foot in the depression between the first and second metatarsals, anterior to their junction and lateral to the extensor pollicis longus tendon, is used in TCM to regulate liver qi and address emotional and cognitive dysfunction. For AD and MCI, Taichong may be stimulated alone or in combination with Hegu via a 0.5-inch perpendicular needle insertion with balanced supplementation and drainage, twisted at 180°±5° at a rate of 50 twists per minute (17). This approach supports emotional stability and cognitive function, aligning with Western understandings of neuroregulation. The Taixi point (KI3), located on the medial ankle in the depression between the medial malleolus and Achilles tendon, is used in TCM to nourish kidney essence and support brain function. In the context of AD and MCI, it is believed to enhance cognitive resilience. The technique involves a 0.5- to 1-inch perpendicular needle insertion with balanced supplementation and drainage, twisted at 180°±20° at 60–90 twists per minute (8). These acupuncture points collectively form a cohesive strategy for addressing neurodegenerative conditions such as AD and MCI, as illustrated in Figure 1.

Figure 1 The anatomical locations of the principal acupuncture points referenced in the literature. KI3, Taixi acupoint; LI4, Hegu acupoint; LR3, Taichong acupoint.

In summary, acupuncture appears to enhance structural and functional plasticity in the aging brain, potentially boosting cognitive function. Yet, its broader impact on AD and MCI, especially the shared and distinct neural mechanisms involved, remains insufficiently explored. Importantly, the reliability of rs-fMRI measures, such as test–retest reliability, is crucial for capturing the interindividual differences in functional networks and ensuring reproducibility, as low reliability can inflate sample size requirements and limit effect detection. To clarify these effects, we employed an activation likelihood estimation (ALE) meta-analysis to pinpoint brain regions activated in patients with AD or MCI following acupuncture. A comparative analysis of these meta-analytic activation maps was then conducted to assess the common and unique neural pathways underlying acupuncture’s therapeutic influence on these conditions. We present this article in accordance with the PRISMA reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1047/rc).

Methods

Literature search and study selection

Two independent reviewers (C.F. and X.L.) systematically searched five comprehensive electronic databases—PubMed, PsycINFO, Google Scholar, SinoMed, and China National Knowledge Infrastructure (CNKI)—from their inception through January 2025, capturing the full spectrum of relevant literature up to this cutoff date. To identify studies investigating acupuncture’s neural effects on AD or MCI via functional neuroimaging, the following keyword search strategy was employed: (“acupuncture” OR “acupoint” OR “needle”) AND (“mild cognitive impairment” OR “Alzheimer’s disease”) AND (“functional magnetic resonance imaging” OR “functional connectivity”). This structured query was tailored to balance sensitivity and specificity, maximizing the retrieval of pertinent studies while minimizing irrelevant results. To ensure consistency and resolve any discrepancies in study selection or data interpretation, a third reviewer (J.Z.W.) adjudicated conflicts, providing an additional layer of oversight to enhance the reliability of the process.

Inclusion and exclusion criteria

The meta-analysis included randomized controlled trials (RCTs) and prospective case–control studies involving participants diagnosed with AD or MCI according to well-established diagnostic criteria, including Petersen’s criteria, the National Institute on Aging-Alzheimer’s Association (NIA-AA) guidelines, the Diagnostic and Statistical Manual of Mental Disorders (DSM)-V, or other recognized standards, ensuring a consistent and reliable participant pool reflective of these neurodegenerative conditions. The interventions assessed focused exclusively on acupuncture treatment administered via manual needling, electroacupuncture, or related techniques, while control groups received sham acupuncture (e.g., superficial needling at nonacupoints), placebo acupuncture (e.g., blunt needles), or no acupuncture intervention, providing a robust basis for evaluating acupuncture’s specific effects. To be included in the analysis, studies were required to report brain activation coordinates in either Talairach or Montreal Neurological Institute (MNI) reference spaces, enabling precise mapping of neural outcomes critical to the ALE analysis. Exclusion criteria were rigorously applied to maintain methodological integrity: case reports lacking group-level statistics were omitted due to their limited generalizability, animal studies were excluded to focus solely on human neural responses, and studies with inaccessible data—despite attempts to contact authors—were disregarded to ensure data availability. Additionally, to avoid duplication bias, multiple publications derived from the same dataset were treated as a single study, with only the most comprehensive or recent report included, which helped to preserve the independence and validity of the analyzed evidence.

Search results

The systematic search yielded 309 records. After deduplication and preliminary screening based on titles and abstracts, 229 articles were assessed in full. A rigorous evaluation followed to determine each study’s adherence to the predefined inclusion criteria, after which 45 studies were excluded: 23 studies did not report coordinates necessary for spatial analysis, 12 lacked the required experimental data, 7 did not conduct whole-brain analyses, and 4 failed to meet the specific inclusion criteria related to the research question and methodological quality.

Ultimately, 13 studies met the criteria and were included in the qualitative synthesis (meta-analysis). These studies collectively provided a robust evidence base to address the primary research objectives.

Characteristics of the included studies

Among the 13 studies included (18-30), 2 were RCTs and 10 were case-control studies. All studies specified clear inclusion and exclusion criteria. Ten studies used DSM-IV dementia criteria, one used Chinese guidelines for dementia and cognitive disorders (10), and two used amnestic MCI criteria (18). Participants were primarily recruited from hospitals, while controls were recruited from communities. All 13 studies used manual acupuncture. The most frequently used acupuncture points included KI3, LR3, and LI4 (Hegu). Nine studies involved single-treatment sessions, while four employed multiple treatments per week over 4, 12, or 16 weeks (17,19). Details on the commonly used acupuncture points and study characteristics are provided in Table 1.

Coding of the literature

The literature was coded based on author name, publication year, sample size, coordinate space, imaging modality, specific contrasts, and coordinate values. The first author K.W. performed the coding at two separate time points, and the corresponding author X.L. verified the coding. The consistency between the two rounds of coding was high, with only minor discrepancies. A summary of the included studies’ basic information is presented in Table 2.

ALE

The ALE method, widely used in neuroimaging meta-analyses, was applied to model the uncertainty of activation foci localization via Gaussian probability density distributions (30). Data processing was conducted with GingerALE software version 3.0.2. Talairach coordinates were converted to MNI space. Separate meta-analyses were performed for AD and MCI, with family-wise error (FWE) correction for multiple comparisons at P<0.05 and a cluster-forming threshold of P <0.001 (5,000 permutations), achieving >80% post hoc power for detected effects based on simulation estimates. A contrast analysis was conducted at P <0.01 with a minimum cluster size of 200 mm³ (10,000 permutations). Cluster sizes are reported with 95% confidence intervals derived from permutation distributions.

Results

Single meta-analyses

The meta-analysis of the 13 included studies revealed that acupuncture increased activation in the right superior frontal gyrus [Brodmann area (BA) 10], the left cerebellar sublobe, the left posterior cerebellar lobe, and the right inferior occipital gyrus (BA 19) in patients with AD as compared to healthy controls (Figure 2 and Table 3); in contrast, decreased functional connectivity was observed in the right middle frontal gyrus (BA 6) (Figure 3, Table 4).

Figure 2 Areas of increased activity in patients with Alzheimer’s disease. (A) Right superior frontal gyrus (BA 10), (B) sublobar left cerebrum, (C) posterior lobe of the right cerebellum, and (D) inferior occipital gyrus of the right cerebrum (BA 19). BA, Brodmann area.

Figure 3 Reduced activity in the middle frontal gyrus of the right cerebrum (BA 6) in patients with Alzheimer’s disease. BA, Brodmann area.

In addition, acupuncture was associated with increased activation in the right superior temporal gyrus (BA 38), right parahippocampal gyrus (BA 28), cerebellar tonsils of both posterior cerebellar lobes, right middle temporal gyrus (BA 21), bilateral posterior cerebellar lobes (declive), left occipital lingual gyrus (BA 18), left superior parietal lobe (BA 7), and the left posterior central gyrus of the parietal lobe (BA 3) in individuals with MCI (Figure 4, Table 5). Reduced connectivity was found in the bilateral posterior cerebellar lobes (inferior semilunar lobule), right posterior cerebellar declive, left precentral gyrus (BA 4) of the frontal lobe, right transverse temporal gyrus (BA 42), right postcentral gyrus (BA 3) of the parietal lobe, and right superior frontal gyrus (BA 6) (Figure 5 and Table 6).

Figure 4 Areas of increased activity in patients with mild cognitive impairment. (A) A parahippocampal gyrus of the right cerebrum (BA 28); (B) cerebellar tonsil of the left cerebellum; (C) cerebellar tonsil of the right cerebellum; (D) middle temporal gyrus of the right cerebellum (BA 21); (E) posterior lobe of the right cerebellum (declive); (F) superior parietal lobule of the left cerebrum (BA 7); (G) lingual gyrus of the left cerebrum (BA 18); (H) posterior lobe (declive) of the left cerebellum; (I) postcentral gyrus of the left cerebrum (BA 3); (J) postcentral gyrus of the left cerebrum (BA 3). BA, Brodmann area.

Figure 5 Regions of reduced activity in patients with mild cognitive impairment. (A) Inferior semilunar lobule of the right cerebellum; (B) declive of the right cerebellum; (C) precentral gyrus of the left cerebrum (BA 4); (D) transverse temporal gyrus of the right cerebrum (BA 42); (E) postcentral gyrus of the right cerebrum (BA 3); (F) inferior semilunar lobule of the left cerebellum; and (G) superior frontal gyrus of the right cerebrum (BA 6). BA, Brodmann area.

Combined analysis

Both patients with AD and individuals MCI exhibited increased activation in the posterior cerebellar tonsils bilaterally, right inferior occipital gyrus (BA 19), right parahippocampal gyrus (BA 28), left superior parietal lobe (BA 7), right middle temporal gyrus (BA 21), bilateral posterior cerebellar lobes (declive), right superior frontal gyrus (BA 10), and the left cerebellar sublobe (Figure 6 and Table 7) as compared to controls; in contrast, decreased connectivity was observed in the right superior frontal gyrus (BA 6), right middle frontal gyrus (BA 6), right posterior cerebellar lobe (inferior semi-lunar lobule), right postcentral gyrus (BA 3) of the parietal lobe, right posterior cerebellar declive, left inferior frontal gyrus (BA 47), right transverse temporal gyrus (BA 42), and left precentral gyrus (BA 4) (Figure 7, Table 8). The research findings and key results are summarized in Table 9.

Figure 6 Regions showing increased activity in both patients with Alzheimer’s disease and those with mild cognitive impairment. (A) Cerebellar tonsil of the right cerebellum. (B) Inferior occipital gyrus of the right cerebrum (BA 19). (C) Parahippocampal gyrus of the right cerebrum (BA 28). (D) Middle temporal gyrus of the right cerebrum (BA 21). (E) Cerebellar tonsil of the left cerebellum. (F) Superior frontal gyrus of the right cerebrum (BA 10). (G) Superior parietal lobule of the left cerebrum (BA 7). (H) Posterior lobe (declive) of the left cerebellum. (I) Posterior lobe (declive) of the right cerebellum. (J) Sublobar region of the left cerebrum. BA, Brodmann area.

Figure 7 Regions showing reduced activity in patients with AD and those with MCI. (A) Frontal gyrus of the right cerebrum superior (BA 6). (B) Middle frontal gyrus of the right cerebrum (BA 6). (C) Inferior semilunar lobule of the right cerebellum. (D) Postcentral gyrus of the right cerebrum (BA 3). (E) Declive of the right cerebellum. (F) Transverse temporal gyrus of the right cerebrum (BA 42). (G) Precentral gyrus of the left cerebrum (BA 4). AD, Alzheimer’s disease; BA, Brodmann area; MCI, mild cognitive impairment.

Discussion

Our meta-analysis provides evidence that acupuncture may enhance brain functional connectivity in patients with AD or MCI, offering insights into its therapeutic potential across these neurodegenerative conditions. By integrating single and combined analyses, our results showed that both shared and distinct neural responses, highlighting acupuncture’s promise as a nonpharmacological intervention to mitigate cognitive decline.

In patients with AD, heightened activation was found in the right superior frontal gyrus (BA 10), left cerebellar sublobe, right posterior cerebellar lobe, and right inferior occipital gyrus (BA 19). The right superior frontal gyrus contributes to executive functioning and social cognition, while the inferior occipital gyrus supports visual processing. These findings suggest that acupuncture may enhance complex cognitive capacities and visuospatial abilities commonly impaired in AD (31). This pattern aligns with prior neuroimaging work associating frontal and occipital changes with improvements in attention and perception in neurodegenerative conditions, although interpretation requires caution and correlation with clinical outcomes. By contrast, reduced activity in the right middle frontal gyrus (BA 6), a region implicated in the executive control network (ECN) and motor planning, points to limitations in acupuncture’s ability to restore motor-related functions (32). The combination of increased activity in cognitive areas with decreased activity in motor regions suggests a selective targeting of higher-order cognitive deficits, although further research is needed to substantiate these interpretations (33).

In patients with MCI, we found increased activation in the right parahippocampal gyrus (BA 28), bilateral posterior cerebellar tonsils, right middle temporal gyrus (BA 21), bilateral posterior cerebellar declive, left occipital lingual gyrus (BA 18), left superior parietal lobe (BA 7), and left posterior central gyrus (BA 3) (34). Many of these regions map onto large-scale networks disrupted in MCI. Specifically, the parahippocampal and middle temporal gyri are associated with the DMN, crucial for episodic memory and language, while the superior parietal lobe is part of the ECN, supporting attention and spatial orientation. The lingual gyrus further contributes to visual integration, often interacting with both DMN- and ECN-related functions. This pattern suggests that acupuncture may promote compensatory recruitment within these networks, thereby enhancing memory retrieval and sensory integration. However, whether such compensation can meaningfully delay dementia progression remains uncertain and must be tested against longitudinal clinical outcomes (35). Conversely, decreased activation in the bilateral posterior cerebellar lobes (inferior semilunar lobule), right transverse temporal gyrus (BA 42), right postcentral gyrus (BA 3), and left precentral gyrus (BA 4) highlights persistent vulnerabilities in sensorimotor and auditory pathways. These reductions suggest that acupuncture’s modulatory effects may not extend uniformly across all functional domains but instead preferentially target higher-order networks (DMN and ECN) rather than primary sensorimotor systems. This asymmetry emphasizes the need for cautious interpretation and further investigation of how acupuncture influences the interplay among the DMN, salience network (SN), and ECN in individuals with MCI.

Comparative analyses revealed distinct neural signatures of acupuncture across disease stages. In patients with AD, activation was concentrated in the right superior frontal gyrus, right inferior occipital gyrus, and left cerebellar sublobe, implicating networks associated with executive control, visual processing, and cerebellar-mediated cognitive regulation—functions critical for maintaining independence at advanced disease stages (36). In contrast, patients with MCI exhibited more robust activation in the parahippocampal gyrus, superior parietal lobe, and middle temporal gyrus, suggesting enhanced memory consolidation, spatial orientation, and sensory processing—domains vulnerable in early decline. These divergent patterns not only reflect disease progression but also underscore the potential for tailoring acupuncture to stage-specific deficits, amplifying its clinical effect. However, our findings also revealed areas of reduced brain activity that temper these benefits. In patients with AD, the most notable decline occurs in the right middle frontal gyrus (BA 6), which is linked to executive planning and motor coordination, suggesting that acupuncture may fall short in reversing these impairments—a limitation consistent with reports of persistent motor deficits in patients with AD despite interventions (37). Similarly, in individuals with MCI, diminished activity in the right posterior cerebellar semilunar lobule, right postcentral gyrus (BA 3), right transverse temporal gyrus (BA 42), and left precentral gyrus (BA 4) indicates incomplete efficacy in restoring auditory, language, and motor functions, aligning with evidence of cerebellar and sensorimotor vulnerabilities in early neurodegeneration (38,39). These reductions highlight the need for a balanced appraisal of acupuncture’s scope, as its strengths in cognitive enhancement should be recognized in addition to its limitations in motor and sensory restoration.

Importantly, while neuroimaging studies can discern noteworthy activation patterns, clinical validation is essential. There is a growing body of research suggesting that acupuncture-induced changes in functional connectivity are associated with improvements in pain, mood, and cognitive function across a variety of conditions (e.g., chronic pain, depression, and insomnia) (40,41). This type of clinical data links neural effects to functional outcomes and may aid in the effective application of acupuncture in AD and MCI. Beyond network-level effects, acupuncture also influences systemic pathways: it exerts anti-inflammatory activity, balances sympathetic and parasympathetic activity, and modulates the hypothalamic-pituitary-adrenal (HPA) axis (42,43). These mechanisms, which are being increasingly implicated in AD and MCI, contribute to disease progression via neuroinflammation, autonomic imbalance, and HPA axis dysregulation. Thus, the brain activation patterns identified in our analysis may reflect only a portion of a broader integrative impact, in which acupuncture influences both central and peripheral processes that converge on cognitive resilience. These results provide critical insights into the neural mechanisms driving acupuncture’s therapeutic effects, enriching our understanding of how this traditional practice modulates brain function in patients with AD or MCI. By identifying specific brain regions responsive to acupuncture, our study contributes to a deeper understanding of how this traditional therapy influences cognitive and motor functions in neurodegenerative conditions (44). The identification of responsive brain regions—such as the frontal and temporal gyri in cognition or the cerebellar and parietal areas in sensory processing—offers a neurobiological foundation for acupuncture’s role in neuroplasticity, corroborating emerging evidence of its capacity to rewire dysfunctional networks (45).

Our findings are in line with large-scale rs-fMRI studies on MCI, such as those from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which indicate that DMN and ECN disruptions are early markers of cognitive decline. The acupuncture-induced enhancements in DMN regions (e.g., the parahippocampal gyrus) found in our study may counteract these disruptions by modulating spontaneous slow oscillations (SSOs), which underlie the brain’s “dark energy”—the dominant energy consumption for maintaining intrinsic neural activity (46,47). Recently proposed models included a hierarchical organization of multiband SSOs, with lower frequencies supporting long-range integration (e.g., the DMN) and higher bands supporting local processing, suggesting acupuncture’s effects could extend to this dark energy framework (48). This implies broader therapeutic implications and suggests that it may be productive to employ large-scale datasets to examine SSO frequency–specific modulations in AD or MCI.

Despite its strengths, our meta-analysis is not without limitations. First, methodological heterogeneity across included studies, including that related to acupuncture techniques (e.g., manual vs. electroacupuncture), imaging modalities, and participant demographics, might have confounded the synthesis of results and potentially introduced variability or bias into our conclusions. Second, there was a risk of publication bias, as studies reporting significant acupuncture effects are more likely to be published than are those with null or negative outcomes, possibly inflating the perceived benefits. Third, while our findings point to activated brain regions, they fall short of delineating the precise mechanistic pathways through which acupuncture exerts its effects, such as neurotransmitter modulation or inflammatory suppression, precluding causal inference (49). Fourth, the individual studies included in this meta-analysis generally had small sample sizes, which may limit the generalizability and reproducibility of their findings. Small samples in neuroimaging can lead to an increased frequency of false positives or inflated effect sizes, reducing the overall reproducibility across studies (50). However, by aggregating data across 13 studies and 702 participants via ALE meta-analysis, our work enhances reproducibility by identifying consistent patterns of brain activation and connectivity changes induced by acupuncture. This highlights the value of meta-analytic approaches in overcoming sample size limitations and suggests that future large-scale, multi-site studies with optimized data collection are warranted to further validate these results. Fifth, the test–retest reliability of rs-fMRI measures in the included studies was not consistently reported, posing challenges for the interpretation of interindividual differences in acupuncture effects. Reliability in functional connectivity can be suboptimal (e.g., mean intraclass correlation coefficient <0.5 with short scans), particularly in clinical populations such as those with AD or MCI in whom motion artifacts or disease-related variability may reduce stability. This underscores the need for future research to incorporate reliability assessments, such as extended scan durations (e.g., 20–30 min) or multisession designs, to enhance measurement precision and support biomarker development (50). Sixth, while ALE provides robust convergence estimates with FWE corrections, it does not yield traditional effect sizes such as Cohen’s d. To address these shortcomings, future research should employ standardized methodologies, incorporate unpublished data to mitigate bias, and integrate multimodal approaches to clarify acupuncture’s underlying mechanisms.

Conclusions

Acupuncture modulates brain networks in patients with AD or MCI, enhancing activation in the frontal, temporal, parietal, and cerebellar regions involved in cognition and sensorimotor integration. Its effects are more pronounced in MCI, suggesting that neuroplasticity is preserved in those with early-stage disease. Shared and disease-specific neural responses highlight acupuncture’s potential for stage-specific cognitive enhancement. These findings provide quantitative evidence supporting acupuncture as a promising nonpharmacological intervention for cognitive impairment in individuals with neurodegenerative disorders.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1047/rc

Funding: This work was supported by the National Natural Science Foundation of China (No. 82271936) and the Zhejiang Province Traditional Chinese Medicine Youth Talent Project (No. 2022ZQ057).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1047/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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