Search Results (1,203)

Purpose: This study aimed to develop a precise predictive model to assess the risk of radiation pneumonitis (RP) and three-year survival in patients with non-small cell lung cancer (NSCLC) following volumetric modulated arc therapy (VMAT). Radiomics features, ensemble stacking, and explainable artificial intelligence (XAI) were integrated to enhance predictive performance and clinical interpretability. Materials and Methods: A retrospective cohort of 221 NSCLC patients treated with VMAT at Kaohsiung Veterans General Hospital between 2013 and 2023 was analyzed, including 168 patients for RP prediction (47 with ≥grade 2 RP) and 118 patients for survival prediction (34 deaths). Clinical variables, dose–volume histogram (DVH) parameters, and radiomic features (original, Laplacian of Gaussian [LoG], and wavelet filtered) were extracted. ANOVA was used for initial feature reduction, followed by LASSO and Boruta-SHAP for feature selection, which formed 10 feature subsets. The data were divided at an 8:2 ratio into training and testing sets, with SMOTE balancing and 10-fold cross-validation for parameter optimization. Six models—logistic regression (LR), random forest (RF), support vector machine (SVM), k-nearest neighbors (KNN), XGBoost, and Ensemble Stacking—were evaluated in terms of the AUC, accuracy (ACC), negative predictive value (NPV), precision, and F1 score. SHAP analysis was applied to interpret feature contributions. Results: For RP prediction, the LASSO-selected radiomic subset (FR) combined with Ensemble Stacking achieved optimal performance (AUC 0.91, ACC 0.89), with SHAP identifying V40 Firstorder_Min as the most influential feature. For survival prediction, the FR subset yielded an AUC of 0.97, an ACC of 0.92, and an NPV of 1.00, with V10 Wavelet Firstorder_Min as the top contributor. The multimodal subset (FC+R) also performed strongly, achieving an AUC of 0.91 for RP and 0.96 for survival. Conclusions: This study demonstrated the superior performance of radiomics combined with Ensemble Stacking and XAI for the prediction of RP and survival following VMAT in patients with NSCLC. SHAP-based interpretation enhances transparency and clinical trust, offering a robust foundation for personalized radiotherapy and precision medicine. Full article

The gut microbiome is essential for nutrient absorption, immune function, and overall metabolic health. A balanced microbial community allows for the breakdown of carbohydrates, proteins, fats, vitamins, and minerals into maximally absorbed nutrients and provides protection against inflammation. Dysbiosis, or microbial imbalance, disrupts these processes and leads to malabsorption, barrier dysfunction, and toxic metabolite production. These imbalances contribute to a wide variety of diseases, from obesity, diabetes, and cardiovascular disease to anemia, osteoporosis, and nervous system dysfunctions. Advances in sequencing, metabolomics, and functional assays have facilitated an enhanced understanding of the ecological and biochemical complexity of gut microbes. AI-based models are also providing new insights into personalized diet and therapeutic approaches. Through the redefinition of malnutrition and chronic disease within microbial ecology, science proves the potential for engineered probiotics, precision prebiotics, and gut-targeted therapies. These innovations hold the potential to improve global health and propel precision medicine in nutrition. Full article

Canine atopic dermatitis (cAD) is a chronic, pruritic, inflammatory skin disease with complex immunopathogenesis involving dysregulated cytokine networks. In recent years, targeted therapies have transformed the management of cAD by directly or indirectly modulating cytokine activity. Lokivetmab, a monoclonal antibody neutralizing interleukin-31, represents a breakthrough in veterinary dermatology, providing rapid and sustained reduction in pruritus with a favorable safety profile. Janus kinase inhibitors, including oclacitinib and the newer ilunocitinib, act downstream by blocking cytokine signal transduction, offering effective control of both acute and chronic phases of disease. Ciclosporin, a calcineurin inhibitor, remains a valuable immunosuppressant for long-term cAD management, while topical tacrolimus provides localized benefits. Together, these therapies mark a paradigm shift from non-specific immunosuppressants to precision medicine. In this context, precision medicine refers to therapeutic strategies that selectively target key cytokines or intracellular signaling pathways central to the pathogenesis of cAD, such as IL-31 or the JAK/STAT axis. Unlike traditional immunosuppressants such as glucocorticoids, which exert broad and non-selective immune suppression, these agents modulate defined molecular mechanisms, thereby improving efficacy and minimizing adverse effects. Consequently, they enable improved quality of life for affected dogs and their owners. Future strategies will likely focus on patient stratification and personalized approaches based on immunological endotypes. Full article

Esophageal squamous cell carcinoma (ESCC) remains a major global health challenge due to its aggressive nature and frequent late-stage diagnosis. Accurate locoregional staging is critical for guiding appropriate therapy, and endoscopic ultrasound (EUS) has emerged as the preferred modality for assessing tumor depth and regional lymph node involvement. In this narrative review, we provide a comprehensive overview of the role of EUS in the management of ESCC, from initial staging to post-treatment assessment. We discuss its strengths and limitations, particularly in differentiating early-stage disease and in restaging after neoadjuvant therapy. The importance of a multimodal approach—integrating EUS with computed tomography (CT), positron emission tomography (PET), and histologic sampling—is emphasized to improve diagnostic precision. We also explore emerging techniques, such as contrast-enhanced EUS, elastography, and novel therapeutic strategies including immune checkpoint inhibitors and endoscopic mucosal resurfacing. While EUS remains a cornerstone in the management of ESCC, ongoing innovation and integration with personalized medicine are expected to further enhance its clinical impact. Full article

Background and Objectives: Low-grade triple-negative breast carcinomas (LG-TNBCs) represent a rare subset of breast cancers that deviate from the aggressive clinical course typically associated with triple-negative tumors. This narrative review aims to consolidate current knowledge on LG-TNBCs, highlighting their diagnostic features, molecular characteristics, and clinical implications to guide appropriate patient management and prevent overtreatment. Materials and Methods: We conducted a comprehensive narrative review using PubMed/MEDLINE, Embase, and Scopus databases up to September 2025. Search terms included combinations of “triple-negative breast carcinoma”, “low-grade”, “adenoid cystic carcinoma”, “secretory carcinoma”, “acinic cell carcinoma”, “tall cell carcinoma with reversed polarity”, “low-grade adenosquamous carcinoma”, and “fibromatosis-like metaplastic carcinoma.” Studies reporting clinicopathologic, immunohistochemical, or molecular data were included. Results: LG-TNBCs include seven distinct entities: adenoid cystic carcinoma, secretory carcinoma, acinic cell carcinoma, tall cell carcinoma with reversed polarity, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, and mucoepidermoid carcinoma. These neoplasms are characterized by distinct morphologic patterns, specific immunohistochemical profiles, and recurrent molecular alterations such as ETV6-NTRK3 fusions and MYB rearrangements. Despite their triple-negative immunoprofile, they demonstrate indolent clinical behavior with excellent prognosis and low metastatic potential, although local recurrence is reported in variants exhibiting infiltrative, locally aggressive behavior. Conclusions: Recognition of LG-TNBCs is essential to prevent overtreatment and guide personalized patient management. Molecular characterization provides diagnostic confirmation and therapeutic opportunities, particularly for NTRK-fusion-positive tumors treatable with targeted inhibitors, highlighting the importance of precision medicine in rare breast tumors. Full article

Decision-making in modern healthcare increasingly relies on integrating a variety of data sources, including patient demographics, medical imaging, laboratory results, clinical narratives, and temporal data, all of which are difficult for traditional computational methodologies to accurately predict. This paper evaluates the latest methodologies that integrate diverse data types, including photographs, clinical notes, temporal measurements, and structured tables, through techniques such as feature amalgamation, prioritization of essential information, and utilization of graphs. We also assess pre-training, fine-tuning, and comprehensive evaluation of model generation procedures. By synthesizing findings from 50 of 91 peer-reviewed papers published between 2020 and 2024, we demonstrate that the integration of structured and unstructured data significantly improves performance in tasks like diagnosis, prognosis prediction, and personalized treatment. This review combines substantial multimodal datasets and applications across several therapeutic domains while addressing critical issues such as data heterogeneity, scalability, interpretability, and ethical considerations. This paper highlights the transformative potential of multimodal models in improving clinical decision support, providing a framework for future research to advance precision medicine and enhance healthcare outcomes. Full article

Background: CRISPR/Cas genome editing is emerging as a powerful tool in oral and maxillofacial medicine, with potential applications in personalized therapies for conditions that currently lack durable treatments. Objectives: This scoping review aimed to map existing evidence on CRISPR-based applications in oral and maxillofacial fields, rather than to assess treatment effectiveness. Methods: A systematic search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov (2012–2024) identified studies and registered trials involving CRISPR with oral health relevance. Eligible articles included peer-reviewed experimental reports and clinical trials. Results: From 1437 records, 121 studies met inclusion criteria: 106 preclinical reports and 15 clinical or translational studies. Investigated domains included oral cancer therapy, hereditary craniofacial syndromes, regenerative strategies, infectious disease models, and pathogen detection. Early clinical efforts focus mainly on CRISPR-edited T-cell immunotherapies in oncology. Major barriers include off-target effects, delivery challenges, regulatory complexity, and ethical concerns. Conclusions: CRISPR-based bioengineering shows strong promise for precision care in oral and maxillofacial medicine. However, current evidence remains largely preclinical and heterogeneous. No clinical recommendations can yet be made, and translation will depend on rigorous late-phase trials, ethical oversight, and health-economic evaluation. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal human malignancies, with five-year survival rates showing only marginal improvement despite decades of intensive research. Its dismal prognosis reflects a combination of intrinsic biological aggressiveness, late clinical presentation, and marked resistance to standard therapies, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Growing evidence indicates that the microbiome is a modifiable factor influencing the onset, progression, and treatment response of PDAC. Microbial communities originating from the gut, oral cavity, and even the tumor microenvironment can shape carcinogenic pathways, modulate immune activity, and alter the efficacy of chemotherapy and immunotherapy. In addition to bacteria, fungal and viral populations are emerging as relevant contributors within this complex ecosystem. This review provides a comprehensive overview of the current mechanistic and translational evidence linking the microbiome to PDAC biology and therapy. It further explores microbiota-targeted interventions—such as probiotics, postbiotics, engineered bacterial strains, bacteriophages, oncolytic viruses, and fecal microbiota transplantation—as promising adjuncts to conventional treatments. A deeper understanding of host–microbiome interactions could yield novel biomarkers and open innovative avenues for precision medicine in PDAC, ultimately improving patient outcomes and reshaping therapeutic paradigms. Integrating microbiome-based strategies into PDAC management may thus represent a crucial step toward more effective and personalized oncologic care. Full article

Background: Stress-related disorders, including PTSD, acute stress disorders, adjustment disorder, and attachment disorders, arise from complex interactions between genetic susceptibility and environmental stressors. While early environmental factors play a central role in the development of these disorders, there is growing evidence that genetic predisposition also contributes to individual differences in vulnerability and resilience. This narrative review examines current evidence on genetic predisposition and resilience mechanisms in stress-related psychopathology during developmental age. Methods: A literature search was performed using PubMed, Cochrane, MedRxiv, and Medline databases, focusing on studies published between 2010 and 2025, written in English, in the pediatric and adolescent population. Priority was given to original research articles and high-impact reviews. Studies were selected based on relevance to the genetic mechanisms underlying vulnerability and resilience to stress. 71 of 317 were selected. Two hundred forty-six articles were excluded due to a lack of relevance to the topic or because they included an adult population. Results: Polymorphisms and epigenetic modifications in genes involved in hypothalamus–pituitary–adrenal axis (FKBP5, NR3C1, ADCYAP1R1 and ACE), serotoninergic (SLC6A4 and HTR2A), noradrenergic and dopaminergic system (COMT and MAOA), BDNF, estrogen receptor and excitatory amino acid transporters are associated with increased risk of psychopathology following early trauma, but are also implicated in the development of resilience. Conclusions: Genetic factors influence both vulnerability and resilience to stress-related disorders. However, further studies based on the role of genetics are needed to advance precision and personalized medicine, which is still largely underexplored to this day in the field of stress-induced disorders. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by pruritus and eczematous lesions that significantly impacts patient quality of life. This review covers the intricate interplay of barrier dysfunction, immune dysregulation, and microbial dysbiosis in the complex pathophysiology of AD. The roles of epigenetic factors and environmental exposures are also examined. The evolving understanding of these factors has revolutionized AD treatment. Beyond foundational topical agents, the landscape for moderate-to-severe AD treatment is now dominated by highly targeted immunotherapies, such as biologics and Janus Kinase (JAK) inhibitors, that precisely block specific inflammatory pathways. Emerging strategies explore microbiome modulation and vitamin D supplementation. This paradigm shift from broad immunosuppression to precision medicine offers improved disease control and reduced systemic toxicities and enables more personalized AD management, significantly benefiting patients. Full article

Therapeutic innovation in cardiovascular medicine is rapidly overcoming the limitations of conventional strategies, providing more targeted, durable, and multidimensional solutions. Key advances include next-generation lipid-lowering agents such as PCSK9 inhibitors, inclisiran, and bempedoic acid, as well as metabolic drugs like SGLT2 inhibitors, GLP-1 receptor agonists, and dual GIP/GLP-1 agonists, which offer cardiovascular and renal benefits beyond glucose control. At the same time, gene therapies, RNA-based interventions, genome editing tools, and nanocarriers are paving the way for precision medicine tailored to individual patient profiles. In parallel, digital innovations, including artificial intelligence, remote monitoring, and telehealth platforms, are transforming care delivery by enhancing adherence, enabling earlier intervention, and refining risk stratification. Collectively, these developments signify a paradigm shift toward a more personalized, proactive, and systems-based model of cardiovascular care. Full article

The heart’s relentless contractile activity depends critically on mitochondrial function to meet its extraordinary bioenergetic demands. Mitochondria, through oxidative phosphorylation, not only supply ATP but also regulate metabolism, calcium homeostasis, and apoptotic signaling, ensuring cardiomyocyte viability and cardiac function. Mitochondrial dysfunction is a hallmark of cardiomyopathies and heart failure, characterized by impaired oxidative phosphorylation, excessive production of reactive oxygen species (ROS), dysregulated calcium handling, and disturbances in mitochondrial dynamics and mitophagy. These defects culminate in energetic insufficiency, cellular injury, and cardiomyocyte death, driving heart disease progression. Diverse cardiomyopathy phenotypes exhibit distinct mitochondrial pathologies, from acute ischemia-induced mitochondrial collapse to chronic remodeling seen in dilated, hypertrophic, restrictive, and primary mitochondrial cardiomyopathies. Mitochondria also orchestrate cell death and inflammatory pathways that worsen cardiac dysfunction. Therapeutic strategies targeting mitochondrial dysfunction, including antioxidants, modulators of mitochondrial biogenesis, metabolic therapies, and innovative approaches such as mitochondrial transplantation, show promise but face challenges in clinical translation. Advances in biomarker discovery and personalized medicine approaches hold promise for optimizing mitochondrial-targeted therapies. Unlike previous reviews that examined these pathways or interventions individually, this work summarizes insights into mechanisms with emerging therapeutic strategies, such as SGLT2 inhibition in HFpEF, NAD⁺ repletion, mitochondrial transplantation, and biomarker-driven precision medicine, into a unified synthesis. This framework underscores the novel contribution of linking basic mitochondrial biology to translational and clinical opportunities in cardiomyopathy and heart failure. This review synthesizes the current understanding of mitochondrial biology in cardiac health and disease, delineates the molecular mechanisms underpinning mitochondrial dysfunction in cardiomyopathy and heart failure, and explores emerging therapeutic avenues aimed at restoring mitochondrial integrity and improving clinical outcomes in cardiac patients. Full article

Introduction: Colonic lipomas (CLs) are benign neoplasms originating from adipose tissue within the gastrointestinal tract. They are often asymptomatic, but in certain cases, patients may present with gastrointestinal bleeding or symptoms related to intestinal obstruction. We report the cases of 18 patients undergoing both surgical and endoscopic resection of colonic lipomas. Given the variability in symptoms, lesion size, and patient demographics, the management of CLs represents a clinical scenario where treatment must be tailored to the individual, aligning with the principles of personalized medicine. This study aims to clarify the clinical and morphological factors guiding treatment selection for colonic lipomas, emphasizing a personalized approach to management. Materials and Methods: We retrospectively reviewed a prospectively collected database of 18 patients with histological diagnosis of colon lipoma after both endoscopic and surgical resection at the Campus Bio-Medico University Hospital, Rome, from 2016 to the first months of 2025. Results: The average patient age was 66 years, and the average maximum size of lipoma was 2.87 cm. The anatomical location of lipomas is very varied, ranging from the ileocecal valve to the distal sigma, and most procedures were endoscopic. Conclusions: Despite the fact that no established guidelines about the management of the CLs are reported in literature, the different approaches are related to symptomatology. Our findings try to clarify and demonstrate how the therapeutic decision, whether endoscopic or surgical, is personalized based on the patients and their clinical condition, illustrating how CL management reflects the broader framework of personalized medicine. Our work confirms that the patients most prone to intussusception phenomena are young women with large colonic lipomas. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management. Full article

The global spread of carbapenem-resistant Acinetobacter baumannii (CRAB) poses a severe public health threat, driving growing interest in phage-based precision antibacterial strategies. This systematic review synthesizes recent advances in the field of A. baumannii phage. Modern taxonomy, based on whole-genome phylogeny, has reclassified the majority of A. baumannii phages into the class Caudoviricetes, revealing distinct evolutionary clades that correlate with host tropism and biological properties, superseding the traditional morphological families (Myoviridae, Siphoviridae, Podoviridae). To overcome limitations of natural phage therapy, such as narrow host range, cocktail therapies (ex vivo resistance mutation rates < 5%) and phage-antibiotic synergism (enabling antibiotic efficacy at 1/4 minimum inhibitory concentration) have significantly enhanced antibacterial efficacy. Preclinical models demonstrate that phage therapy efficiently clears pathogens in pneumonia models and promotes the healing of burn wounds and diabetic ulcers via immunomodulatory mechanisms. Technical optimizations include nebulized inhalation delivery achieving 42% alveolar deposition, and thermosensitive hydrogels enabling sustained release over 72 h. Genetic engineering approaches, such as host range expansion through tail fiber recombination and CRISPR/Cas-mediated elimination of lysogeny, show promise. However, the genetic stability of engineered phages requires further validation. Current challenges remain, including limited host spectrum, the absence of clinical translation standards, and lagging regulatory frameworks. Future efforts must integrate metagenomic mining and synthetic biology strategies to establish a precision medicine framework encompassing resistance monitoring and personalized phage formulation, offering innovative solutions against CRAB infections. Full article