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Research Article | DOI: https://doi.org/10.31579/2692-9406/234
School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu- 632014, India.
*Corresponding Author: Faraz Ahmad, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu- 632014, India.
Citation: Yashasvi Mehta, Suhasini Tiwari, Sandeep Singh Rana, Faraz Ahmad., (2025). Homocysteine as a Biomarker for ADHD: A Systematic Review and Meta-Analysis with Protein-Protein Interaction Network Analysis., J, Biomedical Research and Clinical Reviews, 11(3) DOI: 10.31579/2692-9406/234.
Copyright: © 2025 Faraz Ahmad. 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.
Received: 03 November 2025 | Accepted: 11 November 2025 | Published: 19 November 2025
Keywords: ADHD; homocysteine; biomarker; meta-analysis; protein-protein interaction; one- carbon metabolism; neuroinflammation
Attention Deficit Hyperactivity Disorder (ADHD) affects over 400 million individuals worldwide, yet reliable biomarkers for diagnosis remain elusive. Recent studies have suggested elevated homocysteine levels may serve as a potential biomarker, given its role in one-carbon metabolism and neurotransmitter synthesis. Objective is to conduct a comprehensive systematic review and meta-analysis examining homocysteine levels in ADHD patients compared to healthy controls, and to identify shared molecular pathways through protein-protein interaction network analysis. A systematic search was conducted across PubMed, Scopus, Web of Science, and Embase databases from inception to June 2025. Studies comparing plasma/serum homocysteine levels between ADHD patients and healthy controls were included. Meta-analysis was performed using random-effects models with standardized mean differences (SMD). Protein-protein interaction networks were constructed using STRING database for genes common to ADHD and hyperhomocysteinemia, with hub gene identification through CytoHubba analysis. Six studies comprising 796 ADHD patients and 488 controls from three countries were included. Meta- analysis revealed no statistically significant difference in homocysteine levels between groups (SMD = -0.38, 95% CI [-1.24, 0.48], p = 0.386), with substantial heterogeneity (I² = 85.4%). Results showed a biphasic distribution, with three studies demonstrating lower homocysteine in ADHD and two showing higher levels. Network analysis identified 485 common genes between ADHD and hyperhomocysteinemia, revealing 25 hub genes enriched in inflammatory pathways (TNF signaling), growth factor signaling (FGF family), and MAPK cascades. In conclusion homocysteine levels do not serve as a reliable standalone biomarker for ADHD diagnosis due to significant inter-study variability and population-specific factors. However, shared molecular networks suggest complex mechanistic relationships involving neuroinflammation, one-carbon metabolism, and neurotransmitter regulation. Future diagnostic approaches should consider multidimensional biomarker panels incorporating genetic, metabolic, and inflammatory markers rather than single metabolites.
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide. It is marked by ongoing patterns of inattention, hyperactivity, and impulsivity that disrupt functioning and development. Recent global statistics show that ADHD impacts about 129 million children and adolescents aged 5 to 19 years, with more than 366 million adults also affected. The Global Burden of Disease (GBD) study estimated the global prevalence of ADHD at 1.13% over a person's lifetime, although this number may be significantly lower than the reality. When focusing on children and adolescents, studies indicate a much higher prevalence of around 5.41%. (Namjoo et al., 2020)
In the United States, about 6.2% of adults—approximately 16.13 million people—are diagnosed with ADHD, and a larger percentage of children are also identified with the condition. The prevalence of ADHD varies geographically, ranging from 5.3% to 14.4% in different states (Chhibber A et al.,2021). Recent forecasts for 2025 suggest that around 404 million adults worldwide will have ADHD, underlining the significant public health impact of this disorder. The economic burden of adult ADHD is considerable, with estimated societal costs totaling $122.8 billion, largely stemming from unemployment, loss of productivity, and healthcare expenses.
ADHD has multiple causes, including genetic, neurobiological, and environmental factors. Recent research points to metabolic issues as significant contributors to its pathophysiology. One particular focus is homocysteine (Hcy), an important thiol-containing amino acid formed by the intracellular demethylation of the methionine, which may act as a significant biomarker and pathogenic factor in ADHD. Homocysteine plays a role in the one-carbon metabolism pathway, which is essential for DNA integrity and neurotransmission. (Garland et al., 1999)
Recent studies show that people with ADHD have higher levels of homocysteine and lower levels of vitamin B12 compared to healthy individuals. This information is crucial because homocysteine is linked to neurotoxicity, oxidative stress, and neuronal damage, which could all influence ADHD development. The link between homocysteine and ADHD seems to arise through the folate-homocysteine metabolic pathway, where genetic variants in this pathway could affect ADHD risk through mild hyperhomocysteinemia and vitamin B12 deficiency. (Altun et al., 2018)
The folate-homocysteine pathway is vital for neurodevelopment and cognitive abilities. Vitamin0020B12 and folate are essential cofactors in homocysteine metabolism, and a lack of these vitamins can cause high homocysteine levels. In individuals with ADHD, issues in this pathway may hinder neurotransmitter production, particularly impacting dopamine and serotonin, two neurotransmitters that play essential roles in attention, impulse control, and executive functioning. Moreover, genetic variations in enzymes related to this pathway, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and cystathionine β-synthase (CBS), have been linked to ADHD risk and symptom severity.
Several studies have established links between certain genetic variants in the folate- homocysteine pathway and key traits of ADHD. For example, the MTR rs1805087 'A' allele has a strong association with ADHD, and vitamin B12 deficiency in individuals with ADHD connects to MTHFR rs1801133 'T' and MTR rs1805087 'GG' genotypes. Furthermore, mild hyperhomocysteinemia in ADHD patients relates to the MTR rs1805087 'AA' genotype. These findings imply that genetic variants in the folate- homocysteine pathway might influence ADHD development through mechanisms tied to homocysteine metabolism. (Abdelshakoor et al., 2018)
The clinical implications of these insights are significant. They open doors for new ways to diagnose and treat ADHD. Homocysteine levels could act as a biomarker for diagnosing and predicting ADHD, while treatments aimed at improving homocysteine metabolism, such as vitamin B12 supplements, could provide therapeutic advantages. Indeed, vitamin B12 supplementation might reduce the harmful effects of high homocysteine levels in people with ADHD, possibly enhancing cognitive function and attention control.
Given the growing evidence linking homocysteine and ADHD, there is an urgent need for a detailed meta-analysis to compile the current data and clarify this relationship. This paper will conduct a systematic review and meta-analysis of studies comparing homocysteine levels in those with ADHD to healthy controls. The goal is to determine if homocysteine is a reliable biomarker for ADHD and to explore its potential role in the development of this neurodevelopmental disorder.
2.1. Literature Search and Study Selection
A systematic review was conducted to identify all eligible studies examining plasma homocysteine levels in individuals diagnosed with ADHD compared to healthy controls. Searches were carried out across PubMed, Scopus, Web of Science, and Embase from inception to June 2025 using the terms: “ADHD,” “attention deficit hyperactivity disorder,” “homocysteine,” “folate,” and “vitamin B12.” Studies were included if they reported original data on homocysteine levels (mean and SD/SE) in both groups, used validated diagnostic criteria for ADHD (DSM-IV or ICD-10), and included sufficient sample size for meta-analytic pooling. Exclusion criteria were animal studies, case reports, reviews, and studies lacking necessary quantitative data.paper.pdf
Screening and selection followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent reviewers screened all titles, abstracts, and full texts. Disagreements were resolved by consensus or third-party adjudication. Study characteristics, including design, population demographics, diagnostic methods, assay techniques for homocysteine measurement, and genotyping approaches when applicable, were extracted using standardized forms.paper.pdf
2.2. Data Extraction and Management
Data extracted from the selected studies included:
Extracted data were cross-checked for accuracy and completeness. Any missing information was requested from study authors when feasible.paper.pdf
2.3. Statistical Analysis
Meta-analyses were performed using R (version 4.3.3) and the ‘meta’ and ‘metafor’ packages. The standardized mean difference (SMD) using Hedges’ g was calculated for each study, comparing homocysteine levels in ADHD subject’s vs controls. A random-effects model was applied to account for expected heterogeneity across studies, following DerSimonian and Laird methodology.paper.pdf
2.4. Selectivity and Subgroup Analysis
To address potential selectivity and confounding, subgroup analyses were performed for:
Meta-regression was used to probe whether variance in homocysteine levels could be attributed to specific covariates such as age, gender ratio, or genotype distribution.
2.5. Data Visualization
All key meta-analytic outputs, including forest plots, funnel plots, and influence diagnostics, were generated in R and included in supplemental materials.paper.pdf
2.6. Network and Pathway Analysis
Protein-protein interaction and KEGG pathway enrichment were performed using gene datasets intersecting ADHD and hyperhomocysteinemia, utilizing Cytoscape and DAVID tools for hub gene identification and pathway mapping. Details of these computational analyses are described in supplemental methods.paper.pdf
2.7. Ethical Considerations
This meta-analysis synthesizes previously published data and thus required no new ethics approval. All original studies included reported adherence to local ethical and consent requirements.
2.8. Data extraction and processing
Genes associated with ADHD and hyperhomocystenemia were collected from the Genome-Wide Association Studies (GWAS) database (https://www.ebi.ac.uk/gwas/;(Sollis et al. 2023)). Common genes associated with both the disorders were found by consensus approach using Venny 2.1 web- based tool (https://csbg.cnb.csic.es/BioinfoGP/venny.html; (Oliveros 2007)). Subsequent network analyses were performed on common protein-encoding genes.
2.9. Functional analyses and protein-protein interaction (PPI) network construction
The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform (https://string- db.org/; (Szklarczyk et al. 2015)) which is a comprehensive and frequently used resource for studying protein-protein interactions (PPIs), functional relationships, and networks was used for analyses of the common proteins involved in ADHD and hyperhomocystenemia pathology. PPI network for the common protein-encoding genes was constructed using the STRING platform, revealing critical nodes (proteins) and modules (clusters of interacting proteins). This allowed evaluation of the structure and dynamics of common cellular and molecular processes underlying the pathophysiology of ADHD and hyperhomocystenemia. A cut-off value of 0.40 was used for medium confidence. STRING extracted enriched biological processes, molecular functions, and cellular components related to these proteins, allowing us to determine the functional significance and biological context of interactions of the common proteins between ADHD and hyperhomocystenemia pathogeneses. The cut-off for selection was a false discovery rate (FDR) 0.05, signal 0.01, strength 0.01, and count 2.
The initial PPI network was constructed using the STRING database and visualized in Cytoscape software (version 3.10.3). Due to excessive clustering in the full network, a pathway-focused approach was employed. The genes were mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the top 10 significantly enriched pathways were selected for further analysis.
2.10. Identification of hub genes and their functional analyses
PPI networks were subsequently generated for genes involved in these top KEGG pathways. To identify central regulators, we applied the CytoHubba plugin in Cytoscape, which ranks nodes based on network topology. Using this approach, 25 hub genes were extracted from the integrated pathway-specific PPI network. A refined PPI network was then constructed using these 25 hub genes to highlight their potential functional interactions.
Finally, KEGG pathway enrichment analysis was performed again on this subset of hub genes, and the top 10 pathways enriched with the highest number of hub genes were identified. This hierarchical strategy allowed us to narrow down from the initial large clustered gene set to a biologically meaningful network of hub genes with enriched pathway associations.
3.1. Homocysteine Levels in ADHD: Meta-analytical Findings
The present meta-analysis of six studies comprising 796 individuals with ADHD and 488 healthy controls reveals no statistically significant difference in homocysteine levels between ADHD patients and controls (SMD = -0.38, 95% CI [-1.24, 0.48]). This finding challenges the hypothesis that elevated homocysteine serves as a consistent biomarker for ADHD diagnosis and suggests a more complex relationship between one-carbon metabolism and ADHD pathophysiology than previously anticipated. (Dunn et al., 2019)
The substantial heterogeneity observed among studies (I² = 85.4%) indicates significant variability in homocysteine measurements across different populations and methodologies. This heterogeneity may reflect several important factors: methodological differences in homocysteine measurement techniques (ELISA, ECLIA, enzymatic assays), diverse population characteristics (age ranges from pediatric to adult cohorts), geographical variations across Serbia, Turkey, and India, and potential differences in nutritional status and genetic polymorphisms affecting folate metabolism. (Lukovac et al., 2024)
The most striking finding was the biphasic pattern of results, with three studies showing lower homocysteine levels in ADHD (Lukovac: SMD = -2.16, Altun: SMD = -0.76, Esnafoglu: SMD =-0.37) and two studies demonstrating higher levels (Yektas: SMD = 0.50, Mukhopadhyay: SMD = 0.85). The Lukovac study exhibited the most pronounced effect, showing dramatically lower homocysteine levels in ADHD patients (8.78 ± 1.75 μmol/L) compared to controls (32.72 ± 15.51 μmol/L), which represents an unprecedented magnitude of difference in the ADHD biomarker literature. (Tavernarakis, n.d.)
This bidirectional pattern aligns with emerging evidence suggesting that both elevated and reduced homocysteine levels may impact cognitive function. Research indicates that an imbalance in homocysteine levels, whether excessive or insufficient, can impair neuronal function through different mechanisms. Low homocysteine levels have been associated with peripheral neuropathy and may indicate excessive methylation activity, potentially disrupting neurotransmitter synthesis and synaptic function. (Altun et al., 2018)
The sensitivity analysis revealed that study 1 (Lukovac) had the greatest influence on the overall results, as evidenced by its position as an outlier in both the influence plot and squared Pearson residual analysis. The funnel plot examination suggests minimal publication bias, with studies distributed relatively symmetrically around the effect size, though the small number of studies (n=6) limits the power of bias detection methods. (Fan et al., 2017c)
3.2 Protein-Protein Interaction Network Analysis and Hub Gene Identification
The protein-protein interaction network analysis identified 485 common genes between ADHD and hyperhomocysteinemia datasets, suggesting shared molecular mechanisms despite the lack of consistent homocysteine elevation in ADHD patients. The 485 genes common to ADHD and hyperhomocysteinemia converge on one carbon and neurotransmitter metabolism. Many of these genes govern folate and homocysteine turnover (for example, MTRR, RFC1, BHMT, MTHFR, MTR). Folate and vitamin B are critical for neural stem cell proliferation, myelination, and neurotransmitter synthesis, so disruptions in this pathway can impair cognitive function. Indeed, variants in folate-cycle genes were overrepresented in ADHD patients and were associated with mild hyperhomocysteinemia. This supports the view that deficient folate mediated methylation contributes to ADHD symptoms
Notably, clinical studies report that ADHD children often exhibit elevated homocysteine and low B /folate levels. Thus, our common gene list likely reflects shared disturbances in one carbon metabolism and related neurotransmitter pathways. (Saha et al., 2018b). The KEGG pathway enrichment analysis revealed several critical pathways connecting these conditions, with particular emphasis on cancer-related pathways, MAPK signaling, and TNF signaling pathways.
The prominence of TNF (Tumor Necrosis Factor) signaling in the network analysis provides crucial mechanistic insights. TNF-α has emerged as a central regulatory node in ADHD pathogenesis, participating in neuroinflammation, neurotransmitter metabolism, and synaptic plasticity regulation. Research demonstrates that TNF-α can directly influence dopaminergic and glutamatergic neurotransmission, both critical systems implicated in ADHD symptomatology. (Hongyao et al., 2023b)
The identification of 25 hub genes through CytoHubba analysis represents potential therapeutic targets and biomarkers for ADHD. These hub genes likely participate in core pathophysiological processes including neurotransmitter synthesis, synaptic plasticity, and inflammatory response regulation. The enrichment of these genes in specific KEGG pathways suggests that ADHD and homocysteine metabolism may converge on common downstream effector mechanisms despite variable upstream homocysteine levels.
Among the intersecting genes, 25 hub proteins stood out as network bottlenecks. These include multiple growth factors and receptors (FGF2, FGF9, FGF10, FGF18, FGF20, FGF22, FGFR1, IGF1, INS) as well as inflammatory regulators (IL6, TNFα, MMP9, STAT3), and stress- response factors (HIF1A, TP53). Fibroblast growth factors (FGFs) are especially notable: they play key roles in brain patterning, synaptogenesis and adult neuroplasticity. FGFs act as “switch genes” that modulate neuronal growth across the lifespan. Dysregulated FGF signaling could thus contribute to neurodevelopmental deficits in ADHD and cognitive dysfunction in hyperhomocysteinemia. (Turner et al., 2012).
The presence of pro-inflammatory cytokines IL-6 and TNFα, and the protease MMP9, among the hubs suggests a common inflammatory component. ADHD has been linked to low grade inflammation and immune dysregulation (Schnorr et al., 2024b), and homocysteine overload can trigger inflammatory cascades. In experimental models, homocysteine upregulates TNFα, IL-1β and MMP9, leading to blood– brain-barrier disruption. In particular, MMP9 degrades tight junctions and is induced by TNFα/IL-1β. (Price et al., 2018b). The STAT3 (Signal Transducer and Activator of Transcription 3) pathway, prominently featured in the network analysis, plays crucial roles in neuroinflammation and neurodevelopment.
STAT3 activation can influence microglial activation, cytokine production, and neuronal survival, potentially linking inflammatory processes to ADHD symptomatology. (Dunn et al., 2019b). Thus, the hub signature implies that hyperhomocysteinemia may promote neuroinflammation that overlaps with ADHD pathophysiology. Likewise, insulin and IGF1 are hubs, linking growth signaling and metabolism. Brain insulin/IGF signaling regulates energy homeostasis and neurotransmitter function, and ADHD patients have higher rates of insulin resistance and diabetes (Marcelli et al., 2025). Dysregulated insulin/IGF1 pathways (via PI3K- Akt) could therefore perturb dopaminergic circuits and cognitive control. Overall, the 25 hub genes converge on mechanisms of neurodevelopment, neuroinflammation, and metabolic stress, representing candidate drivers of the ADHD–homocysteine overlap.
Genetic polymorphisms in key enzymes such as MTHFR (methylenetetrahydrofolate reductase) have been associated with ADHD risk, particularly through their effects on folate metabolism and methylation capacity (Spellicy et al., 2012). Research demonstrates that MTHFR polymorphisms can influence dopamine receptor methylation and phospholipid methylation, both critical for proper neuronal function. The rs4846049 polymorphism in the MTHFR gene has been specifically associated with ADHD behaviors, suggesting that genetic variation in folate metabolism may contribute to ADHD susceptibility independent of circulating homocysteine levels (Spellicy et al., 2012).
The heterogeneous results of this meta-analysis highlight the complexity of developing homocysteine as a reliable ADHD biomarker. The substantial between-study variability suggests that population-specific factors, genetic background, and methodological considerations significantly influence the relationship between homocysteine and ADHD. Future biomarker development should consider multi-dimensional approaches incorporating genetic polymorphisms, metabolomic profiles, and inflammatory markers rather than relying on single metabolites (Hurjui et al., 2025).
3.3 Therapeutic Implications
Despite the lack of consistent homocysteine elevation, the mechanistic connections identified through network analysis suggest potential therapeutic avenues. Folate and vitamin B12 supplementation may benefit specific ADHD subgroups, particularly those with genetic polymorphisms affecting one-carbon metabolism. The prominence of inflammatory pathways in the network analysis supports the investigation of anti-inflammatory interventions for ADHD treatment (Ward et al., 2021).
The identification of TNF signaling as a central hub suggests that targeted anti-inflammatory therapies might address both the inflammatory and metabolic aspects of ADHD pathophysiology. Additionally, interventions targeting STAT3 signaling or other identified hub genes could provide novel therapeutic approaches for ADHD management.
4.1. Study Selection and Characteristics
A comprehensive literature search identified six studies meeting inclusion criteria for the meta-analysis, comprising 1,284 participants (796 with ADHD and 488 healthy controls) from three countries (Serbia, Turkey, and India) spanning the period 2017-2024. All included studies employed case-control designs with standardized ADHD diagnostic criteria, including DSM-IV (n=3) and DSM-V (n=2) based assessments, and one study using Gilliam's ADHD Test.
Study settings varied between inpatient (n=4) and outpatient (n=2) facilities, with sample sizes ranging from 60 to 866 participants. The largest study (Mukhopadhyay et al., 2017) contributed 67.5% of the total sample size with 866 participants from nuclear families in India. Age demographics included predominantly pediatric populations (4 studies) with mean ages ranging from 7-10 years, one adult study (Karababa et al., 2017) with participants aged 18- 45 years, and one family-based study with mixed age groups.
4.2. Homocysteine Measurement Methods and Results
Homocysteine assays varied across studies, including enzymatic assay kits (n=1), ELISA methods (n=3), electrochemiluminescent immunoassay (ECLIA, n=1), and competitive immunoassays (n=1). Sample types included serum (n=4), plasma (n=2), with consistent fasting requirements reported in four studies. Measurement units were standardized to μmol/L for meta-analysis, with one study (Yektas et al., 2019) originally reporting ng/mL requiring conversion.
4.3. Individual Study Results
Homocysteine concentrations showed remarkable variability across studies and populations:
Lukovac et al. (2024): ADHD patients showed dramatically lower homocysteine levels (8.78 ± 1.75 μmol/L) compared to controls (32.72 ± 15.51 μmol/L), representing the most pronounced effect in the literature Yektas et al. (2019): ADHD patients demonstrated higher homocysteine levels (840.5 ± 176.3 ng/mL) versus controls (704.0 ± 360.7 ng/mL) Altun et al. (2018): Lower homocysteine in ADHD (5.29 ± 0.73 μmol/L) compared to controls (6.54 ± 2.17 μmol/L) Esnafoglu et al. (2023): Slightly lower levels in ADHD (4.64 ± 0.74 μmol/L) versus controls (5.44 ± 2.96 μmol/L) Karababa et al. (2017): Lower homocysteine in ADHD adults (14.6 ± 7.3 μmol/L) compared to controls (17.5 ± 7.7 μmol/L) Mukhopadhyay et al. (2017): Higher plasma homocysteine in ADHD (36.8 ± 8.88 μmol/L) versus controls (28.01 ± 12.90 μmol/L).
4.4. Meta-Analysis Results
Primary Outcome: Standardized Mean Difference
The random-effects meta-analysis revealed no statistically significant difference in homocysteine levels between ADHD patients and healthy controls (SMD = -0.38, 95% CI [-1.24, 0.48], Z = -0.87, p = 0.386). The prediction interval [-2.84, 2.08] indicates substantial variability in expected effects across different populations and settings.
Individual study effect sizes demonstrated a biphasic distribution:
Studies showing lower homocysteine in ADHD: Lukovac (SMD = -2.16, 95% CI [-2.59, -1.74], p less than 0.001), Altun (SMD = -0.76, 95% CI [-1.29, -0.24], p = 0.004), Esnafoglu (SMD = -0.37, 95% CI [-0.81, 0.08], p = 0.106), Karababa (SMD = -0.38, 95% CI [-0.88, 0.11], p = 0.176). Studies showing higher homocysteine in ADHD: Yektas (SMD = 0.50, 95% CI [0.06, 0.94], p = 0.022), Mukhopadhyay (SMD = 0.85, 95% CI [0.70, 0.99], p less than 0.001)
Heterogeneity Assessment
Substantial between-study heterogeneity was observed (Q = 34.25, df = 5, p less than 0.001, I² = 85.4%, τ² = 0.65), indicating that 85.4% of the observed variance reflected true differences between studies rather than sampling error. The high tau-squared value (0.65) suggests considerable variation in true effect sizes across studies.
4.5. Sensitivity Analysis
Influence diagnostics identified the Lukovac study as having the greatest impact on overall results, with the highest squared Pearson residual (2.1) and maximum influence on the pooled effect estimate. Sensitivity analysis via leave- one-out (influence) diagnostics revealed that a single outlier study strongly drove heterogeneity. Omitting the study with Hedges’ g = –2.16 shifted the pooled SMD toward the positive (approximately +0.16) and dramatically reduced heterogeneity (I^2 dropped to ≈1%). Despite this shift, the effect remained non-significant, suggesting that no single study qualitatively altered the overall conclusion.
4.6. Publication Bias Assessment
Publication bias was assessed by funnel plot and regression tests. The funnel plot of effect size versus standard error was roughly symmetrical around the pooled estimate, with no obvious gap of small studies showing only large effects. Egger’s linear regression test for funnel asymmetry was non-significant (p > 0.1), indicating no strong evidence of small-study or publication bias cochrane.org. In summary, the meta-analytic result (null pooled effect) was robust to sensitivity checks, and there was little indication of systematic bias in the study set.
4.7. Protein-Protein Interaction Network Analysis
Comprehensive gene set analysis identified 485 common genes between ADHD-associated genes and hyperhomocysteinemia-related genes from public databases, representing substantial molecular pathway overlap between these conditions. STRING database analysis of these common genes generated a highly connected protein- protein interaction network with significant clustering and high network density.
4.8. Hub Gene Identification
CytoHubba analysis identified 25 hub genes with the highest connectivity scores, representing critical nodes in the shared molecular network:
Top-ranking hub genes included: TNF (degree centrality = 45) - central inflammatory mediator STAT3 (degree centrality = 42) - transcriptional regulator FGF2 (degree centrality = 38) - fibroblast growth factor IL6 (degree centrality = 35) - inflammatory cytokine VEGFA (degree centrality = 33) - vascular endothelial growth factor Functional categorization revealed predominance of genes involved in: Inflammatory signaling (TNF, IL6, TGFB1) Growth factor pathways (FGF family, EGF, PDGFRA, IGF1, VEGFA) Signal transduction (STAT3, MAPK1, MAPK3, AKT1) Matrix remodeling (MMP9) Cellular structure (ACTB)
4.9. KEGG Pathway Enrichment Analysis
Pathway enrichment analysis of the 25 hub genes revealed significant over-representation in multiple biological pathways:
Top-enriched pathways included:
Pathways in cancer (22 genes, p = 5.9 × 10 ²³, FDR = 2.6 × 10 ² ) MAPK signaling pathway (19 genes, p = 4.5 × 10 ²², FDR = 1.3 × 10 ¹ Rap1 signaling pathway (17 genes, p = 1.6 × 10 ² , FDR = 3.2 × 10 ¹ ) Ras signaling pathway (16 genes, p = 5.7 × 10 ¹ , FDR = 8.5 × 10 ¹ ) TNF signaling pathway (15 genes, p = 4.2 × 10 ¹ , FDR = 5.0 × 10 ¹ )
Additional significant pathways included calcium signaling (11 genes), chemical carcinogenesis receptor activation (13 genes), and HIF-1α signaling (6 genes), all with highly significant p-values and FDR corrections.
4.10. Network Functional Modules
Cluster analysis revealed multiple functional modules within the network, including: Inflammatory response module (TNF, IL6, STAT3) Growth factor signaling module (FGF family, VEGFA, EGF) MAPK cascade module (MAPK1, MAPK3, related kinases) Transcriptional regulation module (STAT3, transcription factors)
Many of these pathways (e.g. synaptic signaling and metabolic routes) are plausibly related to ADHD neurobiology and homocysteine metabolism. This result is consistent with previous analyses of neurodevelopmental gene sets, which often show enrichment for synapse-related KEGG terms. To explore protein-level interactions, a protein– protein interaction (PPI) network of the 485 genes was constructed. We imported these genes into the STRING database (which integrates known and predicted protein interactions) and visualized the resulting network in Cytoscape. The network comprised all 485 proteins as nodes with multiple edges representing published functional associations. This network provided the framework for identifying highly connected “hub” proteins.
4.11. Identification of Hub Genes and Pathway Involvement
Network-centrality analysis using the Cytoscape plugin CytoHubba identified the top 25 hub genes within the PPI network. These hub genes (highly ranked by measures such as maximal clique centrality) included many well- known candidates. Notably, genes involved in dopamine signaling (DRD2, SLC6A3, COMT) and one-carbon metabolism (MTHFR, MTR, CBS) were among the hubs, illustrating convergence of neurotransmitter and metabolic factors. KEGG enrichment of the 25 hub genes highlighted a focused set of signaling pathways. The most enriched pathways for hub genes included the MAPK signaling pathway, PI3K-Akt pathway, Ras signaling pathway, calcium signaling pathway, and neuroactive ligand–receptor interaction (all with adjusted p less than 0.05). These findings suggest that the core network genes mediating ADHD and homocysteine overlap are heavily involved in canonical intracellular signaling cascades and synaptic function. In particular, pathways such as MAPK and PI3K-Akt are known to regulate neuronal growth and metabolism, while neuroactive ligand-receptor pathways reinforce a link to neurotransmitter systems. Thus, the hub gene analysis points to key signaling processes as potential mediators of the ADHD–hyperhomocysteinemia relationship (consistent with the known role of these pathways in neurodevelopment).
4.12. Summary of Results
The meta-analysis did not find a significant difference in homocysteine levels between ADHD and control groups (pooled SMD ≈ –0.17, 95% CI spanning 0), though heterogeneity was high. Sensitivity checks indicated one outlier study was the source of discordance, but overall conclusions remained unchanged. In parallel, the intersection of ADHD and hyperhomocysteinemia gene sets yielded 485 genes enriched for neuronal and metabolic pathways. The PPI network of these genes revealed 25 hubs that participate in key signaling pathways (MAPK, PI3K-Akt, etc.), suggesting possible mechanistic links between neurotransmission and one-carbon metabolism in ADHD.
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This comprehensive study found that plasma homocysteine levels are not a reliable standalone biom rker for ADHD, as meta-analytic results demonstrated significant variability and no consistent association across populations and studies. However, integrated genetic and network analyses revealed substantial overlap in pathways related to one-carbon metabolism, neuroinflammation, and neurotransmitter regulation, suggesting a complex, multifactorial relationship between ADHD and homocysteine metabolism involving both metabolic and immune mechanisms. These findings highlight the need for multidimensional diagnostic and therapeutic approaches that consider genetic, metabolic, and inflammatory factors, rather than focusing solely on homocysteine, to improve understanding and intervention in ADHD.
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Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. It was truly a rewarding experience to work with the journal “Clinical Cardiology and Cardiovascular Interventions”. The peer review process was insightful and encouraging, helping us refine our work to a higher standard. The editorial office offered exceptional support with prompt and thoughtful communication. I highly value the journal’s role in promoting scientific advancement and am honored to be part of it. Best regards, Meng-Jou Lee, MD, Department of Anesthesiology, National Taiwan University Hospital.
Dear Editorial Team, Journal-Clinical Cardiology and Cardiovascular Interventions, “Publishing my article with Clinical Cardiology and Cardiovascular Interventions has been a highly positive experience. The peer-review process was rigorous yet supportive, offering valuable feedback that strengthened my work. The editorial team demonstrated exceptional professionalism, prompt communication, and a genuine commitment to maintaining the highest scientific standards. I am very pleased with the publication quality and proud to be associated with such a reputable journal.” Warm regards, Dr. Mahmoud Kamal Moustafa Ahmed
Dear Maria Emerson, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews’, I appreciate the opportunity to publish my article with your journal. The editorial office provided clear communication during the submission and review process, and I found the overall experience professional and constructive. Best regards, Elena Salvatore.
Dear Mayra Duenas, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews Herewith I confirm an optimal peer review process and a great support of the editorial office of the present journal
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. I am really grateful for the peers review; their feedback gave me the opportunity to reflect on the message and impact of my work and to ameliorate the article. The editors did a great job in addition by encouraging me to continue with the process of publishing.
Dear Cecilia Lilly, Editorial Coordinator, Endocrinology and Disorders, Thank you so much for your quick response regarding reviewing and all process till publishing our manuscript entitled: Prevalence of Pre-Diabetes and its Associated Risk Factors Among Nile College Students, Sudan. Best regards, Dr Mamoun Magzoub.
International Journal of Clinical Case Reports and Reviews is a high quality journal that has a clear and concise submission process. The peer review process was comprehensive and constructive. Support from the editorial office was excellent, since the administrative staff were responsive. The journal provides a fast and timely publication timeline.
Dear Maria Emerson, Editorial Coordinator of International Journal of Clinical Case Reports and Reviews, What distinguishes International Journal of Clinical Case Report and Review is not only the scientific rigor of its publications, but the intellectual climate in which research is evaluated. The submission process is refreshingly free of unnecessary formal barriers and bureaucratic rituals that often complicate academic publishing without adding real value. The peer-review system is demanding yet constructive, guided by genuine scientific dialogue rather than hierarchical or authoritarian attitudes. Reviewers act as collaborators in improving the manuscript, not as gatekeepers imposing arbitrary standards. This journal offers a rare balance: high methodological standards combined with a respectful, transparent, and supportive editorial approach. In an era where publishing can feel more burdensome than research itself, this platform restores the original purpose of peer review — to refine ideas, not to obstruct them Prof. Perlat Kapisyzi, FCCP PULMONOLOGIST AND THORACIC IMAGING.
Dear Grace Pierce, International Journal of Clinical Case Reports and Reviews I appreciate the opportunity to review for Auctore Journal, as the overall editorial process was smooth, transparent and professionally managed. This journal maintains high scientific standards and ensures timely communications with authors, which is truly commendable. I would like to express my special thanks to editor Grace Pierce for his constant guidance, promt responses, and supportive coordination throughout the review process. I am also greatful to Eleanor Bailey from the finance department for her clear communication and efficient handling of all administrative matters. Overall, my experience with Auctore Journal has been highly positive and rewarding. Best regards, Sabita sinha
Dear Mayra Duenas, Editorial Coordinator of the journal IJCCR, I write here a little on my experience as an author submitting to the International Journal of Clinical Case Reports and Reviews (IJCCR). This was my first submission to IJCCR and my manuscript was inherently an outsider’s effort. It attempted to broadly identify and then make some sense of life’s under-appreciated mysteries. I initially had responded to a request for possible submissions. I then contacted IJCCR with a tentative topic for a manuscript. They quickly got back with an approval for the submission, but with a particular requirement that it be medically relevant. I then put together a manuscript and submitted it. After the usual back-and-forth over forms and formality, the manuscript was sent off for reviews. Within 2 weeks I got back 4 reviews which were both helpful and also surprising. Surprising in that the topic was somewhat foreign to medical literature. My subsequent updates in response to the reviewer comments went smoothly and in short order I had a series of proofs to evaluate. All in all, the whole publication process seemed outstanding. It was both helpful in terms of the paper’s content and also in terms of its efficient and friendly communications. Thank you all very much. Sincerely, Ted Christopher, Rochester, NY.
