2025-09-26 2025, Volume 4 Issue 3

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  • research-article
    Tushar Menon, Vipan Chahil, Dhruv Patel, Corina Grancorvitz, Krishnaswami Vijayraghavan

    Inflammation is a fundamental driver of atherosclerotic cardiovascular disease (ASCVD), orchestrating immune activation, endothelial dysfunction, and plaque instability. While lipid-lowering therapies can reduce the burden of ASCVD, persistent inflammation remains a critical determinant of residual cardiovascular risk, highlighting the need for deeper investigation into inflammatory pathways. Key mediators, including interleukin-6, high-sensitivity C-reactive protein, and myeloperoxidase, amplify immune cell infiltration, foam cell formation, and extracellular matrix degradation, exacerbating atherosclerotic progression. Beyond these well-established markers, emerging inflammatory biomarkers, such as cluster of differentiation (CD)47, serum and glucocorticoid-regulated kinase 1 (SGK1), P-selectin, and growth differentiation factor 15 (GDF15), provide novel insights into vascular inflammation and immune dysregulation. CD47 modulates macrophage-mediated immune evasion, allowing apoptotic debris to accumulate within plaques, while SGK1 enhances pro-inflammatory signaling and endothelial dysfunction. P-selectin facilitates leukocyte adhesion and platelet aggregation, contributing to plaque destabilization and thrombotic risk. GDF15, a stress-responsive cytokine, is associated with adverse cardiovascular outcomes, linking metabolic dysfunction to chronic inflammation. Likewise, inflammasome activation, particularly through NACHT, LRR, and PYD domains-containing protein 3 and absent in melanoma 2 pathways, triggers cytokine cascades that perpetuate vascular injury, while clonal hematopoiesis of indeterminate potential promotes myeloid-driven inflammation and atherosclerotic acceleration. The expanding role of these biomarkers underscores the complexity of inflammation in ASCVD and highlights their potential for refining cardiovascular risk assessment and elucidating novel mechanisms underlying plaque progression.

  • research-article
    Tushar Menon, Vipan Chahil, Dhruv Patel, Corina Grancorvitz, Krishnaswami Vijayraghavan

    Inflammation plays a central role in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs), contributing to plaque progression, instability, and thrombosis. Chronic systemic inflammation exacerbates endothelial dysfunction, promotes oxidative stress, and accelerates atherogenesis, necessitating targeted interventions. This review explores established and emerging strategies for modulating inflammation to improve cardiovascular outcomes. Statin therapy remains foundational, with trials, such as JUPITER, demonstrating significant reductions in cardiovascular events through high-sensitivity C-reactive protein modulation, independent of low-density lipoprotein lowering. Non-statin lipid-lowering therapies, including proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, and bempedoic acid, have shown additional anti-inflammatory benefits and further reduce inflammation-driven cardiovascular risk. In addition, triglyceride-lowering agents targeting apolipoprotein C-III and angiopoietin-like protein pathways offer promising avenues for reducing metabolic inflammation and residual ASCVD risk. Anti-inflammatory pharmacotherapy has gained traction, with trials such as canakinumab anti-inflammatory thrombosis outcomes study, colchicine cardiovascular outcomes trial, and low-dose colchicine underscoring the efficacy of canakinumab and colchicine in reducing cardiovascular events. Emerging interleukin (IL) pathways (e.g., IL-17, IL-33, and IL-36) and novel therapeutic targets (e.g., cluster of differentiation 47 inhibitors, serum/glucocorticoid-regulated kinase 1 modulation, and P-selectin blockade) present future opportunities for precision cardiovascular medicine. However, residual inflammatory risk persists despite optimal lipid control, highlighting the need for a multimodal approach integrating lipid-lowering, anti-inflammatory, and targeted immunomodulatory therapies. The expanding role of inflammation in ASCVD suggests a paradigm shift toward inflammation-guided treatment strategies. Further research is warranted to refine patient selection, personalize therapy, and optimize long-term outcomes for inflammation-driven cardiovascular disease.

  • research-article
    Aakarshi Gupta, Praveen Mallari, Tracy Taulier, Mohammad Amjad Kamal

    Electrical stimulation (ES) has emerged as a versatile modality in biomedical research, primarily due to its ability to modulate cellular activities across the cell membrane. As a barrier to electrical signals, the cell membrane plays a crucial role in healing, tissue regeneration, and cancer treatment. This review highlights the cellular processes involved in ES, focusing on the changes within and across the membrane, including effects on proteins, ions, and signaling pathways. ES regulates membrane potential and ion flow, such as calcium and sodium ions, which are essential for intercellular signaling and cell survival. In addition, ES facilitates electroporation, enhancing membrane permeability to allow controlled drug and gene delivery. It also modulates receptor sensitivity and cellular signaling efficiency by altering the lipid bilayer configuration and protein conformation. The applications of ES are extensive, including its use in wound healing, nerve regeneration, and as an adjunct to cancer treatments. Bioelectric Meridian Therapy, a new approach, employs ES for pain control, tissue repair stimulation, and energy flow regulation. Nevertheless, ES faces limitations such as heterogeneity in cellular responses, challenges in determining optimal stimulus parameters, and concerns regarding long-term safety. To address these issues, there is a need for real-time adaptive systems and personalized ES protocols to achieve safety and efficacy in all therapeutic settings. A deeper understanding of ES-cell membrane interactions can improve the current therapeutic paradigm and enhance the effectiveness of ES- based treatments. Further research is necessary to establish patient-specific ES parameters and integrate them into the precision medicine frameworks, minimizing side effects and improving treatment outcomes.

  • research-article
    Alan R. George, Han S. Kim, Carsen R. McDaniel, Richard B. Hill, Albert W. Cheng, Brian W. Stancoven, Claudia P. Millan, Kimberly Ann Inouye, Adam R. Lincicum, Thomas M. Johnson

    Over the past several decades, a trend toward minimally invasive surgery has emerged in various disciplines of medicine and dentistry. In periodontics, one manifestation of this phenomenon is the use of tunneling techniques for mucoperiosteal flap reflection. Tunnel flaps are characterized by the establishment of a space between the alveolar bone or periosteum and the overlying soft tissue while maintaining intact interdental gingiva and/or crestal keratinized mucosa. The oral and facial interdental papillae and col areas remain intact during the procedure. Retaining interproximal tissue integrity may enhance wound stability during early healing, and limited evidence suggests that tunnel flaps can improve several patient-reported outcome measures, such as comfort level, initial esthetics, and time required for return to normal activities. Multiple refinements have been promulgated since the introduction of the first tunneling techniques, and clinical applications have expanded into numerous areas of the field, including surgical treatment of periodontitis, periodontal plastic surgery, and alveolar ridge augmentation. The purpose of this narrative review is to describe the evolution of tunneling techniques over time and suggest opportunities to further develop tunneling applications. Two clinical circumstances are described in which multi-surface tunneling at oral, facial, and proximal tooth surfaces can be employed to achieve favorable clinical and patient-oriented outcomes.

  • research-article
    Farbod Zahedi Tajrishi, Daphne P. Ferdinand, William Herbst, Linda R. Peterson, Keith C. Ferdinand

    Despite decades of progress in prevention and management, cardiovascular disease (CVD) remains the leading cause of mortality in the United States (US) and globally, with persistent and even widening disparities in outcomes across racial, ethnic, geographic, and socioeconomic groups. As a complement to clinical care, community-based interventions have emerged as vital tools in promoting cardiovascular health, particularly in underserved populations. This perspective focuses on recent advances in US-based community interventions for CVD, while acknowledging global relevance, and explores the historical evolution, current landscape, and future directions of community-driven CVD prevention strategies. We highlight foundational models such as the Healthy Heart Community Prevention Project in New Orleans, Louisiana, and examine recent major studies and innovations in the field from the US and across the world. Community-rooted programs demonstrate growing potential to address upstream determinants of cardiovascular health. Their continued success, however, will depend on sustained investment, robust evaluation frameworks, and alignment with clinical care pathways and health policy infrastructure.

  • research-article
    Sergey Suchkov, Robert H. Lustig, Marlene Escobedo-Monge, Sofia Blokh, Natalya Andronova, Olga Goryacheva, Marina Borisovna Moyseyak, Timur Vlasov, Veronika Polyakova, Elena Antonova, Aleksandr Tuykavin

    In the modern era, health is a key element in shaping the trajectory of human civilization. The personalized and precision medicine model is a preventive strategy capable of operating across a wide range of technological applications, from biomarker-driven genomic profiling to determine the characteristics of an individual’s genomic landscape, to combinatorial assessments of the individual’s interaction with the microenvironment for constructing the individual phenotype. Omics technologies demonstrate their multidisciplinary potential in pre-clinical screening, predictive and prognostic diagnosis, multidimensional monitoring, and targeted therapy, through the prism of preventive and curative rehabilitation strategies concerning a particular individual, as well as the principles and resources of genomic biostatistics and molecular epidemiology at the population and national levels. Therefore, this article aims to highlight the omics approach to nutritional assessment and dietary recommendations from the individual to the population level.

  • research-article
    Abel Gallegos, Daniel Nasef, Milan Toma

    Bone fractures represent a significant health burden that demands precise and timely diagnosis to optimize patient outcomes. To address challenges such as data scarcity, overfitting, and generalizability, this study investigates the use of convolutional neural networks (CNNs) for automated fracture detection in X-ray images. A dataset of 4,900 X-ray images was preprocessed and evenly divided into training, validation, and test subsets. The proposed CNN model directly addressed generalizability and overfitting issues by prioritizing training stability and incorporating advanced techniques. These techniques included batch normalization and dropout to enhance stability and mitigate overfitting, with five-fold cross-validation yielding an average accuracy of 95%. Validation and held-out test datasets achieved accuracies of 95.8% and 94.5%, respectively, while external validation on an independent dataset confirmed the model’s generalizability at 91.7%. High recall rates across all datasets underscore the model’s capacity to minimize missed fracture diagnoses, whereas slightly lower precision on external data indicates a need to address false positives. These findings suggest that artificial intelligence is best deployed as a screening tool, serving as an initial triage mechanism that flags potential cases for further human-guided evaluation, thereby enhancing clinical efficiency without replacing the diagnostic expertise of healthcare professionals.

  • research-article
    Hamzeh Almashni, Ruben Leyton, Abdusalam Alrmali, Yousef Amrou, Hom-Lay Wang, Muhammad H. A. Saleh

    Flap design is a key factor in the clinical outcomes of periodontal regeneration (PR). This study compares the effectiveness of minimally invasive flap (MIF) to conventional flap (CF) techniques in PR procedures performed by periodontic residents. The study also addresses how technique sensitivity may influence clinical outcomes when performed by less experienced operators. A retrospective study was conducted on patients who underwent PR from January 2012 to January 2023 at the School of Dentistry, University of Michigan. Flap techniques were classified as MIF or CF, and clinical outcomes, including bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), gingival recession (GR), changes in keratinized gingiva, and tooth loss, were evaluated. Statistical analysis using generalized estimation equations was performed for the overall sample and separately for each group. The study sample consisted of 40 male (45.5%) and 48 female patients (54.5%), with an average age of 63.1 ± 13.8 years and a mean follow-up of 42 months. No significant differences were found between the MIF and CF groups regarding the reduction in PD or GR. However, the CF group exhibited a superior gain in CAL (p=0.005) and a greater decrease in BOP after adjustment for confounders (odds ratio: 4.44, p=0.0276). Tooth type and defect depth were identified as significant factors affecting clinical outcomes. Both techniques were effective in treating periodontal defects. However, the CF approach demonstrated a greater improvement in CAL and BOP. Given the technique-sensitive nature of MIF, the limited clinical experience of resident operators may have contributed to the diminished performance of MIF observed in this study. Simpler surgical techniques may offer comparable effectiveness to more complex, superior surgical techniques in a university-based setting when performed by less experienced operators.

  • research-article
    Jocelyn R. Jensen, Duy Do, Yuan-ping Chang, Sophia Anderson, Matthew D. Carson, Suzanne Dintzis, Richard M. Levenson, Eric J. Seibel

    Breast cancer (BC) is one of the most prevalent malignancies worldwide, with early and rapid diagnosis playing a critical role in improving patient outcomes. Core-needle biopsies (CNBs) are the current gold standard for minimally invasive BC diagnoses. However, in low-resource and rural settings, access to CNB diagnostics is limited by infrastructural constraints, long histopathology turnaround times, as well as financial and geographical barriers. To address these challenges, we developed the CoreView imaging on needle (ION), an affordable, integrated imaging system designed to provide rapid, and point-of-care diagnostic assessment of CNB samples. The CoreView ION integrates microscopy with ultraviolet surface excitation technology, enabling the imaging of tissue biopsy surfaces within 5 min, significantly reducing diagnostic delays. This study presents the design, fabrication, and verification of the CoreView ION prototype operation, including its imaging workflow, staining protocols, and tissue compression testing. Our results demonstrate that the system can successfully generate histology-grade images of porcine and murine fresh biopsies, preserving cellular and nuclear detail of normal and tumor tissue. By streamlining CNB imaging and incorporating mainly manual low-cost components, the CoreView ION has the potential to improve BC diagnostics in low-resource settings, ultimately enhancing early detection and patient care.

  • research-article
    Anssi H. Manninen