Search Results (4,721)

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Background: Electrocardiograms (EKGs) are essential tools in emergency medicine, often used to evaluate chest pain, dyspnea, and other symptoms suggestive of cardiac dysfunction. Yet, EKGs are not universally administered to all emergency department (ED) patients. Understanding and predicting which patients receive an EKG may offer insights into clinical decision making, resource allocation, and potential disparities in care. This study examines whether integrating structured clinical data with free-text patient narratives can improve prediction of EKG utilization in the ED. Methods: We conducted a retrospective observational study to predict electrocardiogram (EKG) utilization using data from 13,115 adult emergency department (ED) visits in the nationally representative 2021 National Hospital Ambulatory Medical Care Survey–Emergency Department (NHAMCS-ED), leveraging both structured features—demographics, vital signs, comorbidities, arrival mode, and triage acuity, with the most influential selected via Lasso regression—and unstructured patient narratives transformed into numerical embeddings using Clinical-BERT. Four supervised learning models—Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF) and Extreme Gradient Boosting (XGB)—were trained on three inputs (structured data only, text embeddings only, and a late-fusion combined model); hyperparameters were optimized by grid search with 5-fold cross-validation; performance was evaluated via AUROC, accuracy, sensitivity, specificity and precision; and interpretability was assessed using SHAP values and Permutation Feature Importance. Results: EKGs were administered in 30.6% of adult ED visits. Patients who received EKGs were more likely to be older, White, Medicare-insured, and to present with abnormal vital signs or higher triage severity. Across all models, the combined data approach yielded superior predictive performance. The SVM and LR achieved the highest area under the ROC curve (AUC = 0.860 and 0.861) when using both structured and unstructured data, compared to 0.772 with structured data alone and 0.823 and 0.822 with unstructured data alone. Similar improvements were observed in accuracy, sensitivity, and specificity. Conclusions: Integrating structured clinical data with patient narratives significantly enhances the ability to predict EKG utilization in the emergency department. These findings support a personalized medicine framework by demonstrating how multimodal data integration can enable individualized, real-time decision support in the ED. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article

Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article

Background/Objectives: Extracellular vesicles (EVs) are involved in cell-to-cell communication and delivery of signaling molecules and represent an interesting approach in targeted therapy. This project focused on EV-mediated facilitation and cell-specific delivery of effector antimiR molecules carried by biologically produced gold nanoparticles (AuNPs). Methods: First, we loaded EVs derived from cancer cells 4T1 with AuNPs-antimiR. The AuNPs were also decorated with or without transferrin (Tf) molecules. We examined parental cell-specific delivery of the AuNPs-Tf-antimiR within monocultures as well as co-cultures in vitro. Subsequently, we used autologous EVs containing AuNPs-Tf-antimiR to target tumor cells in a xenograft tumor model in vivo. Efficacy of the antimir transfer was assessed by qPCR and apoptosis assessment. Results: In vitro, EVs loaded with AuNPs-antimiR were internalized only by the parental cells and the AuNPs-antimiR transfer was successful and effective only in EVs that were decorated with Tf. We achieved effective delivery of the antimiR molecule into cancer cells in vivo, which was proved by specific silencing of the target oncogenic miRNA as well as induction of cancer cells apoptosis. Conclusions: EVs represent an interesting and potent way for targeted cargo delivery and personalized medicine. On the other hand, there are various safety and efficacy challenges that remain to be addressed. Full article

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article