Praveen Kumar Chandra Sekar

Background: Myocardial infarction (MI) is a leading cause of disability and death worldwide. Apolipoprotein E ( APOE ) plays a key role in lipid metabolism, and its genetic polymorphisms have been implicated in atherosclerosis and coronary artery diseases. However, the association between the APOE ε4 polymorphism and MI risk remains inconsistent across populations. Methods: A comprehensive meta-analysis of case–control studies evaluating the association between MI risk and APOE ε4 polymorphisms was conducted in accordance with the PRISMA guidelines. Relevant English-language studies were identified using the PubMed, Web of Science, Google Scholar, and CNKI databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under allelic, dominant, heterozygous, and homozygous genetic models using fixed- or random-effects models, as appropriate. Ethnicity-based subgroup analyses, sensitivity analyses, publication bias assessments, and credibility ceiling analyses were performed to evaluate robustness. Results: A total of 36 eligible studies comprising 13,791 MI cases and 12,854 controls were included in the analysis. Overall analysis showed that the APOE ε4 allele was significantly associated with an increased MI risk (OR = 1.40, 95% CI: 1.22–1.62). Consistent risk-enhancing effects were observed in the dominant, heterozygous, and homozygous models, with evidence of a gene-dose relationship. Subgroup analyses demonstrated a stronger, more consistent association in Asian populations, whereas associations in Caucasian populations were weaker and more heterogeneous. Sensitivity analyses, including the exclusion of studies that deviated from Hardy–Weinberg equilibrium, confirmed the stability of the findings. Egger’s regression test suggested potential publication bias, and trim-and-fill analysis attenuated the pooled effect estimates. Credibility ceiling analysis demonstrated that the overall allelic and dominant associations remained statistically significant across credibility ceilings of up to 20%, supporting the robustness of the observed ε4-related associations. Conclusions: This meta-analysis supports an association between the APOE ε4 polymorphism and increased susceptibility to myocardial infarction, particularly in Asian populations. However, evidence of potential publication bias suggests that the magnitude of this association should be interpreted cautiously and confirmed in future large-scale multiethnic studies.

Introduction: Cancer progression is sustained by complex interactions between oncogenic signaling pathways and immune checkpoint networks, yet their mechanistic crosstalk remains poorly integrated in existing reviews. This review synthesises the bidirectional regulatory relationships between oncogenic signaling and immune checkpoints, with emphasis on mechanistic interdependencies, therapeutic resistance, and precision oncology strategies. Methods: A narrative review of published literature was conducted covering PI3K/AKT/mTOR, RAS/MAPK, and JAK/STAT oncogenic pathways; immune checkpoints including PD-1/PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT; tumour microenvironment interactions; multi-omics integration; pharmacogenomics; and AI-driven drug discovery platforms. Results: Three core crosstalk axes were identified. First, the PI3K/AKT–PD-L1 axis: AKT-mediated GSK-3β inactivation stabilises PD-L1 protein, and PTEN loss constitutively amplifies surface PD-L1 expression, suppressing T-cell cytotoxicity. Second, the MAPK–immune suppression axis: sustained ERK signalling downregulates MHC class I and TAP1/TAP2 components, while BRAF V600E drives secretion of immunosuppressive cytokines including VEGF and IL-10. Third, the JAK/STAT–PD-L1 axis: IFN-γ-driven JAK1/JAK2 activation induces PD-L1 transcription via STAT1, while JAK loss-of-function mutations confer acquired resistance to anti-PD-1 therapy by abrogating MHC-I re-expression. Discussion: These crosstalk mechanisms explain why tumours with high oncogenic signalling burden consistently show attenuated immunotherapy responses and provide the molecular rationale for combination targeting strategies. Multi-omics integration, pharmacogenomic biomarkers including MSI-H status and PIK3CA mutation, and AI-guided modelling frameworks offer structured approaches for translating these findings into clinically actionable patient stratification decisions. Conclusion: Rational combination strategies co-targeting oncogenic signalling and immune checkpoints, guided by multi-omics profiling and biomarker-driven patient stratification, represent the most promising approach for achieving durable precision oncology outcomes.

Objective: To systematically review advances in surgical techniques for secondary cleft palate repair, emphasizing their impact on velopharyngeal function, speech outcomes, and the methodological validity of speech assessments used in published studies . Design: Following PRISMA 2021 guidelines, six electronic databases were searched for articles from January 2012 to February 2025 using MeSH terms related to secondary cleft palate repair, velopharyngeal insufficiency, palatoplasty, and speech outcomes. Eligible studies included clinical reports with ≥10 patients undergoing secondary repair. Data on surgical methods, outcomes, and complications were extracted and qualitatively synthesized due to heterogeneity across studies. Setting: All published clinical studies evaluating secondary cleft palate repair outcomes. Patients/Participants: Individuals presenting with residual velopharyngeal insufficiency, recurrent fistula, or speech dysfunction following primary palatoplasty. Main Outcome Measures: Speech resonance and intelligibility, velopharyngeal closure rate, fistula recurrence, donor-site morbidity, and obstructive sleep apnea risk. Results: Fourteen studies met the inclusion criteria. Palate-based re-repair with Furlow double-opposing Z-plasty and buccal myomucosal flaps improved resonance and closure in small to moderate gaps. Pharyngeal flap and sphincter pharyngoplasty achieved satisfactory closure in larger defects but increased the risk of airway obstruction. However, most studies lacked validated speech protocols or controlled for articulatory errors and fistula effects, limiting confidence in the interpretation of outcomes. Conclusions: While secondary repairs often improve resonance and velopharyngeal competence, evidence remains constrained by heterogeneity and non-validated assessment methods. Future multicenter research integrating standardized, speech pathologist-verified protocols is essential to establish evidence-based algorithms for secondary cleft palate repair.

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease influenced by genetic, environmental, and immunological factors. Variations in cytokine genes, including tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10), have been implicated in SLE pathogenesis, but their associations remain uncertain owing to conflicting study results.Material and Methods: A systematic search of the Google Scholar, PubMed, and Embase databases was conducted to examine TNF-α (rs1800629) and IL-10 (rs1800896) polymorphisms in SLE. Eligible studies were selected based on specific inclusion criteria, and data were independently extracted. Quality assessment was performed using the Newcastle-Ottawa Scale, and the Hardy-Weinberg equilibrium was evaluated. Meta-analyses were conducted using Cochrane Rob Tool 2 and Review Manager version 5.4 to determine odds ratios and 95% confidence intervals.Results: According to the meta-analysis, a significant association was found between SLE risk and TNF-α-308 G/A polymorphism in allelic, dominant, and heterozygote models. However, no association was found between homozygous and recessive models. Interleukin-10 polymorphisms were not significantly associated with SLE risk in any model. Ethnicity-specific analysis revealed a significant association between the TNF-α allele and SLE susceptibility in Asian populations but not in Caucasians.Conclusions: This meta-analysis identified a strong correlation between the TNF-α-308 G/A polymorphism and SLE susceptibility, particularly in Asian populations. However, no association was found between IL-10 polymorphisms and SLE. More extensive studies with diverse populations are required to validate and enhance these findings.

Objective. This narrative review aimed to explore the multifaceted nature of ischemic stroke (IS) and its underlying genetic factors, emphasize the role of genetics in early detection and prevention, and acknowledge the complex influences on stroke prevalence across various countries. Methods. An extensive overview of the causes, mechanisms, and genetics of IS was conducted by reviewing several studies and recent findings. The role of specific genes in monogenic stroke disorders, implications of polygenic influences, recent advances in genetic evaluation, and methods for early IS detection were synthesized and discussed. Results. IS was influenced by genetics, underlying medical conditions, and lifestyle. Specific genes, including NOTCH3, HTRA1, COL3A1, and mtDNA, are involved in monogenic stroke syndromes and predominantly affect younger populations. Polygenic disorders, studied using genome-wide association study and sequencing techniques, play a prominent role in susceptibility to IS. Genetic evaluation has become instrumental in risk prediction, influencing clinical practices and potential therapeutic interventions. Early detection methods, such as enhanced imaging techniques and blood biomarkers, are crucial for managing IS outcomes. Conclusion. Ischemic stroke is a complex disorder with a significant global impact. Understanding its genetic basis promises to improve early detection and effectively establish preventative measures. Although genetic evaluation and innovative detection techniques offer promise, focusing on lifestyle modifications and managing underlying health conditions remains paramount for reducing the incidence and severity of IS. Continuous research and technological advancements are essential for developing personalized medical approaches and improving global healthcare strategies.

Aim: to present literature data on the genetic underpinnings of inflammatory bowel disease (IBD), focusing on key genetic variants such as NOD2, ATG16L1, and IL23R; The objective of this was to understand how these genetic factors contribute to immune dysregulation, epithelial barrier dysfunction, and mucosal homeostasis in IBD.Key points. IBD, encompassing Crohn's disease and ulcerative colitis, is intricately shaped by a nexus of genetic and environmental factors, and its global prevalence is increasing. Genetic research has identified pivotal variants — NOD2, ATG16L1, and IL23R — linked to IBD, influencing key pathways, such as autophagy, interleukin signaling, and bacterial management. These genetic variants, integral to IBD's etiology of IBD, have functional significance because they perturb immune regulation, compromise epithelial barrier integrity, and disrupt mucosal homeostasis, collectively contributing to intestinal inflammation through diverse mechanisms. Early detection of IBD is paramount for arresting disease progression and underscoring the importance of prognostic testing and genetic screening, especially in cases with familial predispositions or very early onset IBD. Additionally, the use of certain IBD medications, such as corticosteroids, azathioprine, and infliximab, may have implications for male fertility, necessitating a nuanced understanding of these potential effects for informed decision-making in IBD management. This comprehensive understanding of the genetic landscape, functional implications, and diagnostic strategies is vital for advancing personalized treatments and improving outcomes in individuals with IBD.Conclusion. IBD is a complex gastrointestinal disorder influenced by a combination of genetic and environmental factors. Genetic variants, including NOD2, ATG16L1, and IL23R, contribute to dysregulation of immune responses, epithelial barrier function, and mucosal homeostasis. While progress has been made in understanding the genetic landscape of IBD, ongoing research is needed to elucidate the functional consequences of these variants, identify causal genes, and explore gene-environment interactions. This deeper understanding holds the potential for more precise diagnostics and personalized treatments, ultimately improving outcomes in individuals living with IBD.

Ischemic heart disease (IHD) is a major global health issue, frequently resulting in myocardial infarction and ischemic cardiomyopathy. Prompt and precise diagnosis is essential to avert complications such as heart failure and sudden cardiac death. Although invasive coronary angiography remains the gold standard for high-risk patients, noninvasive multimodality imaging is becoming more prevalent for those at low-to-intermediate risk. This review evaluated the current state of multimodality imaging in IHD, including echocardiography, nuclear cardiology, cardiac magnetic resonance imaging (MRI), computed tomography (CT) angiography, and invasive coronary angiography. Each modality has distinct strengths and limitations, and their complementary use provides a comprehensive assessment of cardiac health. Integrating artificial intelligence (AI) into imaging workflows holds promise for enhancing diagnostic accuracy and efficiency. AI algorithms can optimize image acquisition, processing, and interpretation of complex imaging data. Emerging technologies like 4D flow MRI, molecular imaging, and hybrid systems [e.g., positron emission tomography (PET)/MRI, PET/CT] integrate anatomical, functional, and molecular data, providing comprehensive insights into cardiac pathology and potentially revolutionizing the management of IHD. This review also explored the clinical applications and impact of multimodality imaging on patient outcomes, emphasizing its role in improving diagnostic precision and guiding therapeutic decisions. Future directions include AI-driven decision support systems and personalized medicine approaches. Addressing regulatory and ethical challenges, such as data privacy and algorithm transparency, is crucial for the broader adoption of these advanced technologies. This review highlighted the transformative potential of AI-enhanced multimodality imaging in improving the diagnosis and management of IHD.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both non-motor and motor symptoms, due to the loss of dopamine-producing neurons in the brain. Monoamine oxidase-B (MAO-B) inhibitors are essential in the treatment of PD, as they increase dopamine levels and could potentially slow down the progression of the disease. MAO-B inhibitors block the ability of the enzyme to degrade dopamine in the brain. MAO-B inhibitors work by inhibiting this enzyme, which raises dopamine levels and helps reduce motor symptoms, such as akinesia and stiffness in the muscles. In addition to their impact on dopamine levels, MAO-B inhibitors may possess neuroprotective properties. Research indicates that these inhibitors can shield neurons from the harmful byproducts of dopamine breakdown, such as dihydroxy acetaldehyde and hydrogen peroxide. This neuroprotective effect could potentially slow the progression of PD and protect against neuronal damage. MAO-B inhibitors are effective in treating both advanced and early stages of PD. They are recommended as initial treatments for individuals with early PD and can also be used as supplementary therapy in advanced PD to assist in managing motor complications. Additionally, MAO-B inhibitors have shown promise for the treatment of non-motor symptoms of PD, such as fatigue and sleep disturbances. MAO-B inhibitors are an important class of drugs for the treatment of PD, offering both symptomatic relief and potential disease-modifying effects. The goal of ongoing research and development of MAO-B inhibitors is to enhance their safety and selectivity profiles, which could lead to improved treatment approaches for PD and other neurodegenerative disorders.