Search Results (1,089)

Finite element (FE) modeling has emerged as a powerful computational approach in cardiovascular biomechanics, enabling detailed simulations of myocardial stress, strain, and hemodynamics, which are challenging to measure with conventional imaging techniques. This narrative review explores the progression of cardiac FE modeling from research-focused applications to its increasing integration into clinical practice. Specific attention is given to the mechanical effects of myocardial infarction, the limitations of conventional LV volume-reduction surgeries, and novel therapeutic approaches like passive myocardial reinforcement via hydrogel injections. Furthermore, the review highlights the critical role of patient-specific FE simulations in optimizing LV assist device parameters and guiding targeted device placements. Cutting-edge developments in artificial intelligence-enhanced FE modeling, including surrogate models and precomputed simulation databases, are examined for their potential to facilitate real-time, personalized therapeutic decision-making. Collectively, these advancements position FE modeling as an essential tool in precision medicine for structural heart disease. Full article

Background/Objectives: Male infertility is a prevalent and often underrecognized manifestation of cystic fibrosis (CF), primarily caused by congenital bilateral absence of the vas deferens (CBAVD) due to CFTR gene mutations. With improved life expectancy in CF patients, reproductive counseling and fertility management have gained clinical relevance. Methods: This narrative review synthesizes current evidence on the genetic underpinnings, diagnostic evaluation, and reproductive management of male infertility in CF and CFTR-related disorders. It also highlights recent advances in assisted reproductive technologies (ART), the role of CFTR modulators, and emerging molecular research. Results: Most men with CF or CBAVD have intact spermatogenesis but present with obstructive azoospermia. Diagnosis relies on clinical examination, semen analysis, genetic testing, and imaging. Sperm retrieval combined with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) achieves high success rates. Genetic counseling is essential to assess reproductive risks and guide partner screening. New therapies—particularly CFTR modulators—have improved systemic health and fertility potential. Future directions include gene therapy, microfluidics-based sperm selection, and personalized molecular strategies. Conclusions: Male infertility in CF represents a treatable consequence of a systemic disease. Advances in reproductive medicine and precision genetics now offer affected men viable paths to biological parenthood while also emphasizing the broader health implications of male infertility. Full article

The evolving paradigm of precision medicine is redefining the landscape of orthobiologic therapies by moving beyond traditional diagnosis-driven approaches toward biologically tailored interventions. This review synthesizes current evidence supporting precision orthobiologics, emphasizing the significance of individualized treatment strategies in musculoskeletal regenerative medicine. This narrative review synthesized literature from PubMed, Embase, and Web of Science databases (January 2015–December 2024) using search terms, including ‘precision medicine,’ ‘orthobiologics,’ ‘regenerative medicine,’ ‘biomarkers,’ and ‘artificial intelligence’. Biological heterogeneity among patients with ostensibly similar clinical diagnoses—reflected in diverse inflammatory states, genetic backgrounds, and tissue degeneration patterns—necessitates patient stratification informed by molecular, genetic, and multi-omics biomarkers. These biomarkers not only enhance diagnostic accuracy but also improve prognostication and monitoring of therapeutic responses. Advanced imaging modalities such as T2 mapping, DTI, DCE-MRI, and molecular PET offer non-invasive quantification of tissue health and regenerative dynamics, further refining patient selection and treatment evaluation. Simultaneously, bioengineered delivery systems, including hydrogels, nanoparticles, and scaffolds, enable precise and sustained release of orthobiologic agents, optimizing therapeutic efficacy. Artificial intelligence and machine learning approaches are increasingly employed to integrate high-dimensional clinical, imaging, and omics datasets, facilitating predictive modeling and personalized treatment planning. Despite these advances, significant challenges persist—ranging from assay variability and lack of standardization to regulatory and economic barriers. Future progress requires large-scale multicenter validation studies, harmonization of protocols, and cross-disciplinary collaboration. By addressing these limitations, precision orthobiologics has the potential to deliver safer, more effective, and individualized care. This shift from generalized to patient-specific interventions holds promise for improving outcomes in degenerative and traumatic musculoskeletal disorders through a truly integrative, data-informed therapeutic framework. Full article

Low back pain (LBP) remains one of the most prevalent and disabling musculoskeletal conditions globally, with profound social, economic, and healthcare implications. The rising incidence and chronic nature of LBP highlight the need for more objective, personalized, and effective approaches to assessment and rehabilitation. In this context, bioengineering has emerged as a transformative field, offering novel tools and methodologies that enhance the understanding and management of LBP. This narrative review examines current bioengineering applications in both diagnostic and therapeutic domains. For assessment, technologies such as wearable inertial sensors, three-dimensional motion capture systems, surface electromyography, and biomechanical modeling provide real-time, quantitative insights into posture, movement patterns, and muscle activity. On the therapeutic front, innovations including robotic exoskeletons, neuromuscular electrical stimulation, virtual reality-based rehabilitation, and tele-rehabilitation platforms are increasingly being integrated into multimodal treatment protocols. These technologies support precision medicine by tailoring interventions to each patient’s biomechanical and functional profile. Furthermore, the incorporation of artificial intelligence into clinical workflows enables automated data analysis, predictive modeling, and decision support systems, while future directions such as digital twin technology hold promise for personalized simulation and outcome forecasting. While these advancements are promising, further validation in large-scale, real-world settings is required to ensure safety, efficacy, and equitable accessibility. Ultimately, bioengineering provides a multidimensional, data-driven framework that has the potential to significantly improve the assessment, rehabilitation, and overall management of LBP. Full article

Over the past decade, patient-derived organoids (PDOs) have emerged as powerful in vitro models that closely recapitulate the histological, genetic, and functional features of their parental primary tissues, representing a ground-breaking tool for cancer research and precision medicine. This advancement has led to the development of living PDO biobanks, collections of organoids derived from a wide range of tumor types and patient populations, which serve as essential platforms for drug screening, biomarker discovery, and functional genomics. The classification and global distribution of these biobanks reflect a growing international effort to standardize protocols and broaden accessibility, supporting both basic and translational research. While their relevance to personalized medicine is increasingly recognized, the establishment and maintenance of PDO biobanks remain technically demanding, particularly in terms of optimizing long-term culture conditions, preserving sample viability, and mimicking the tumor microenvironment. In this context, this review provides an overview of the classification and worldwide distribution of tumor and paired healthy tissue-specific PDO biobanks, explores their translational applications, highlights recent advances in culture systems and media formulations, and discusses current challenges and future perspectives for their integration into clinical practice. Full article

Obesity is a global health challenge marked by substantial inter-individual differences in responses to dietary and lifestyle interventions. Traditional weight loss strategies often overlook critical biological variations in genetics, metabolic profiles, and gut microbiota composition, contributing to poor adherence and variable outcomes. Our primary aim is to identify key biological and behavioral effectors relevant to precision medicine for weight control, with a particular focus on nutrition, while also discussing their current and potential integration into digital health platforms. Thus, this review aligns more closely with the identification of influential factors within precision medicine (e.g., genetic, metabolic, and microbiome factors) but also explores how these factors are currently integrated into digital health tools. We synthesize recent advances in nutrigenomics, nutritional metabolomics, and microbiome-informed nutrition, highlighting how tailored dietary strategies—such as high-protein, low-glycemic, polyphenol-enriched, and fiber-based diets—can be aligned with specific genetic variants (e.g., FTO and MC4R), metabolic phenotypes (e.g., insulin resistance), and gut microbiota profiles (e.g., Akkermansia muciniphila abundance, SCFA production). In parallel, digital health tools—including mobile health applications, wearable devices, and AI-supported platforms—enhance self-monitoring, adherence, and dynamic feedback in real-world settings. Mechanistic pathways such as gut–brain axis regulation, microbial fermentation, gene–diet interactions, and anti-inflammatory responses are explored to explain inter-individual differences in dietary outcomes. However, challenges such as cost, accessibility, and patient motivation remain and should be addressed to ensure the effective implementation of these integrated strategies in real-world settings. Collectively, these insights underscore the pivotal role of precision nutrition as a cornerstone for personalized, scalable, and sustainable obesity interventions. Full article

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies. Full article

Treatment-resistant mental health concerns significantly contribute to society in terms of financial costs and individually by creating emotional and functional costs. An important yet little-recognized cause of treatment-resistant mental health conditions is tetrahydrobiopterin (BH4) deficiency. BH4 is an essential cofactor for producing serotonin, dopamine, norepinephrine, and nitric oxide—molecules critical to mood and focus. The enzyme GTP Cyclohydrolase 1 (GCH1), produced by a gene of the same name, catalyzes the first step in synthesizing BH4. Variants in this gene have been associated with low BH4 levels, as well as depression and ADHD. The case reports presented in this article illustrate that a partial BH4 deficiency, as conveyed by the GCH1 rs841 variant, may contribute to wider issues in mental and neurological health including depression and ADHD but also severe treatment-resistant anxiety, Premenstrual Dysphoric Disorder, insomnia, complex behavioral issues, and autism. The effects of GCH1-mediated BH4 deficiency may be able to be rescued with a low-dose BH4 replacement, as illustrated by these cases, where substantial observational improvements in mental health concerns were reported in all five cases. This paper also demonstrates how a genomics clinical decision support tool can non-invasively flag “low producers” by identifying individuals with the AA genotype for GCH1 rs841, as well as other modifiable genomic contributing factors to mental health concerns. These cases broaden the understanding of BH4′s psychiatric relevance and also serve to further the medical literature by documenting positive responses to low-dose BH4 (ranging from 0.09 to 0.3 mg/kg/day) and other genotype-guided interventions across diverse mental and neurological health presentations, highlighting the potential benefits and importance of a genomically targeted, precision approach to psychiatry. Full article

Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas. Full article

Background: Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) are two common autoimmune disorders for which the choice of drug regimen is clinically crucial. However, due to drug-drug interactions and individual differences, the therapeutic process faces greater risks. Methods: In this study, we propose a drug recommendation model that combines drug combination frequency, risk assessment, and genetic interaction information with the aim of providing personalized, low-risk treatment options for patients with lupus erythematosus and antiphospholipid syndrome. We extracted drug combination frequencies and drug-gene interaction information from data sources, such as the MIMIC-III clinical database, Drug Bank, and Gene Expression Omnibus. The model comprehensively evaluates the frequency of drug combinations, the risk level, and the gene interaction information through a greedy algorithm to recommend the optimal drug alternatives. Results: The experimental results show that the model is able to effectively reduce the potential risk between drugs while ensuring the drug treatment effect. In addition, the performance evaluation of the drug recommendation model shows that the model performs well under different drug combinations and clinical scenarios, and can provide clinicians with effective drug substitution suggestions. Conclusions: This study provides an important theoretical basis and technical support for advancing the realization of personalized therapy and precision medicine. Full article

Bioinks represent the core of 3D bioprinting, as they are the carrier responsible for enabling the fabrication of anatomically precise, cell-laden constructs that replicate native tissue architecture. Indeed, their role goes beyond structural support, as they must also sustain cellular viability, proliferation, and differentiation functions, which are critical for applications in the field of regenerative medicine and personalized therapies. However, at present, a persistent challenge lies in reconciling the conflicting demands of rheological properties, which are essential for printability and biological functionality. This trade-off limits the clinical translation of bioprinted tissues, particularly for vascularized or mechanically dynamic organs. Despite huge progress during the last decade, challenges persist in standardizing bioink characterization, scaling production, and ensuring long-term biomimetic performance. Based on these challenges, this review explores the inherent trade-off faced by bioink research optimizing rheology to ensure printability, shape fidelity, and structural integrity, while simultaneously maintaining high cell viability, proliferation, and tissue maturation offering insights into designing next-generation bioinks for functional tissue engineering. Full article

This review highlights the emerging functional implications of nonsense-mediated mRNA decay (NMD) in human diseases, with a focus on its therapeutic potential for cardiovascular disease. NMD, conserved from yeast to humans, is involved in apoptosis, autophagy, cellular differentiation, and gene expression regulation. NMD is a highly conserved surveillance mechanism that degrades mRNAs containing premature termination codons (PTCs) located upstream of the final exon-exon junction. NMD serves to prevent the translation of aberrant mRNA and prevents the formation of defective protein products that could result in diseases. Key players in this pathway include up-frameshift proteins (UPFs), nonsense-mediated mRNA decay associated with p13K-related kinases (SMGs), and eukaryotic release factors (eRFs), among others. Dysregulation of NMD has been linked to numerous pathological conditions such as dilated cardiomyopathy, cancer, viral infections, and various neurodevelopmental and genetic disorders. This review will examine the regulatory mechanisms by which NMD regulation or dysregulation may contribute to disease mitigation or progression and its potential for cardiovascular disease therapy. We will further explore how modulating NMD could prevent the outcomes of mutations underlying genetically induced cardiovascular conditions and its applications in personalized medicine due to its role in gene regulation. While recent advances have provided valuable insights into NMD machinery and its therapeutic potential, further studies are needed to clarify the precise roles of key NMD components in cardiovascular disease prevention and treatment. Full article

Multiple myeloma (MM) is a malignant plasma cell disorder that evolves from precursor conditions including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding the biological continuum and the molecular drivers of disease progression is crucial for early diagnosis and risk-adapted therapy. Recent advances in next-generation sequencing have identified recurrent mutations in the RAS/MAPK, TP53, and MYC pathways, along with epigenetic alterations that contribute to clonal evolution and therapeutic resistance. Novel diagnostic tools including minimal residual disease (MRD) assessment, gene expression profiling, and advanced imaging have improved risk stratification. Therapeutically, the integration of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has dramatically improved patient outcomes. In parallel, emerging immunotherapies such as CAR-T cells, bispecific T-cell engagers, and antibody–drug conjugates are expanding treatment options, especially in relapsed or refractory settings. Future directions aim to personalize treatment using genomics, target the tumor microenvironment, and leverage synthetic lethality and epigenetic vulnerabilities. This review highlights the evolving landscape of plasma cell disorders from molecular pathogenesis to cutting-edge therapeutic innovations, emphasizing the need for precision medicine approaches to improve survival and quality of life for patients with MM and its precursors. Full article

The increasing demand for high-throughput, real-time, and single-molecule protein analysis in precision medicine has propelled the development of novel sensing technologies. Among these, nanopore-based methods have garnered significant attention for their unique capabilities, including label-free detection, ultra-sensitivity, and the potential for miniaturization and portability. Originally designed for nucleic acid sequencing, nanopore technology is now being adapted for peptide and protein analysis, offering promising applications in biomarker discovery and disease diagnostics. This review examines the latest advances in biological, solid-state, and hybrid nanopores for protein sensing, focusing on their ability to detect amino acid sequences, structural variants, post-translational modifications, and dynamic protein–protein or protein–drug interactions. We critically compare these systems to conventional proteomic techniques, such as mass spectrometry and immunoassays, discussing advantages and persistent technical challenges, including translocation control and signal deconvolution. Particular emphasis is placed on recent advances in protein sequencing using biological and solid-state nanopores and the integration of machine learning and signal-processing algorithms that enhance the resolution and accuracy of protein identification. Nanopore protein sensing represents a disruptive innovation in biosensing, with the potential to revolutionize clinical diagnostics, therapeutic monitoring, and personalized healthcare. Full article

Background/Objectives: Fatigue is a highly prevalent and burdensome symptom among individuals with Marfan syndrome (MFS), yet its heterogeneity and underlying psychosocial and clinical correlates remain underexplored. This study aimed to identify and characterize distinct fatigue-related profiles in MFS patients using a data-driven cluster analysis approach. Methods: A cross-sectional study was conducted involving 127 patients with MFS from a specialized connective tissue disorder center in Italy. Participants completed self-reported measures of fatigue severity (Fatigue Severity Scale, FSS), depressive symptoms (Patient Health Questionnaire-9, PHQ-9), and insomnia (Insomnia Severity Index, ISI). The body mass index (BMI) and clinical data were also collected. A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed to reduce dimensionality, followed by hierarchical clustering (Ward’s method), exploring solutions from k = 2 to k = 10. The optimal cluster solution was identified based on silhouette scores and clinical interpretability. Results: Three distinct clusters emerged: (1) a cluster characterized by low fatigue with minimal psychological and sleep-related symptoms (younger patients, lower PHQ-9 and ISI scores), (2) a cluster characterized by moderate fatigue with moderate psychological and sleep-related symptoms (intermediate age, moderate PHQ-9 and ISI scores), and (3) a cluster characterized by high fatigue with elevated psychological and sleep-related symptoms (older patients, higher PHQ-9, ISI, and FSS scores). Significant differences were observed across clusters in age, BMI, depressive symptoms, insomnia severity, and fatigue levels (all p < 0.05). Conclusions: Our findings highlight the heterogeneity of fatigue experiences in MFS and suggest the importance of profiling patients to guide personalized interventions. This approach may inform precision medicine strategies and enhance the quality of life for individuals with this rare disease. Full article