Search Results (6,677)

Skin aging is a multifactorial process involving structural and functional changes in the dermis. In recent years, the treatment of age-related skin changes in the face, neck, and décolleté has become a growing focus in the fields of esthetic medicine and dermatology. The increasing demand for natural, youthful results without surgical intervention or prolonged downtime has led to the development and widespread application of minimally invasive energy-based technologies, such as High-Intensity Focused Ultrasound (HIFU) and Radiofrequency (RF). The aim of this review is to summarize current evidence regarding the mechanisms of action, clinical efficacy, and safety of HIFU and RF, as well as their combined applications in skin rejuvenation. Relevant studies were selected based on their scientific quality and relevance to the topic. Current evidence indicates that both HIFU and RF promote collagen remodeling and dermal tightening through different energy-delivery mechanisms. Comparative studies suggest that their combined use may enhance esthetic outcomes and improve patient satisfaction. Overall, these technologies represent innovative, non-surgical approaches for facial, neck, and décolleté rejuvenation. Full article

Background/Objectives: Oxford Nanopore sequencing produces long reads quickly, but most functional profiling tools were developed for short reads or rely on assembly pipelines that are computationally costly and sensitive to long-read error rates. We present NanoPrism, a taxonomy-guided pipeline for rapid functional profiling of long-read metagenomes. Methods: NanoPrism (i) identifies sample composition with Kraken2, (ii) constructs compact species-specific coding sequence (CDS)–KEGG ortholog databases, and (iii) estimates ortholog abundances by direct minimap2 alignment of nanopore reads with single-copy marker normalization. We evaluated NanoPrism on simulated Pseudomonas aeruginosa PAO1 and PA14 reads and on ZymoBIOMICS mock-community datasets sequenced on GridION and PromethION platforms. Results: On the Zymo long-read datasets, NanoPrism achieved Pearson correlations of 0.917–0.922 against independent expected ortholog profiles under unit-sum normalization. On matched one-million-read subsets, NanoPrism achieved higher correlations and lower Jensen–Shannon distances and mean absolute errors than the evaluated DIAMOND-based MEGAN-LR workflow. Experiments that omitted one species at a time from the reference database showed that omission of low-abundance community members had limited effects on the aggregate KO profile, whereas omission of the dominant Listeria monocytogenes reference from the Log community reduced Pearson correlation from approximately 0.92 to 0.29. Conclusions: NanoPrism offers a computationally efficient option for taxonomy-guided functional profiling of bacterial isolates and defined microbial communities. Validation on complex clinical and environmental metagenomes, broader forms of taxonomic-classification error, and dedicated fungal benchmarks remain necessary. Full article

Congenital melanocytic nevi (CMN) are pigmented skin lesions present at birth with a variable risk of developing into melanoma over time. The mitogen-activated protein kinase signaling (MAPK) pathway plays a critical role in the development and progression of CMN, making it a key target for therapeutic interventions. Precision medicine aims to optimize therapeutic efficacy while minimizing adverse effects by tailoring treatments to individuals’ genetic and molecular profiles. This literature review examines the potential of precision medicine in managing CMN, with a specific focus on MEK inhibition within the MAPK pathway, summarizing current preclinical and clinical evidence, mechanisms of action, and therapeutic integration with surgical management strategies. Although early results are promising, the need for personalized treatment strategies, informed by genetic testing and biomarker profiling, is emphasized to improve the management of CMN and reduce the risk of malignant transformation. Further research is necessary to establish the long-term safety and effectiveness of MEK inhibition in CMN therapy, which could offer a more targeted and individualized approach to care. Full article

Mesenchymal stem cells (MSCs) are a critical biological resource for regenerative medicine, immunomodulation, and personalized cell therapy. Three structural problems persist: (1) the absence of standardized, quantitative quality indicators; (2) insufficient tamper-proof traceability throughout the manufacturing and banking lifecycle; and (3) the lack of a personalized matching system linking MSC batch characteristics to patient-specific clinical requirements. This paper proposes the MSC Digital Assetization Framework (MDAF), an applied engineering framework that addresses all three problems at the architectural and prototype level. Here, digital assetization—the transformation of a biological product into a structured, traceable, and transferable digital quality record within a multi-institutional trust infrastructure—denotes verifiable, traceable, quality-certified digital recordization of MSC batches, not tokenization or financial trading. The quality engine integrates morphological, FLIM-derived metabolic–proliferative, donor blood panel, flow cytometry, and manufacturing metadata inputs through a bidirectional Cross-Attention fusion module, yielding a continuous MSC quality score (MQS, 0–100) and an S/A/B/C/D five-tier grade. Privacy-preserving verification is implemented via two independent Groth16 zero-knowledge proof circuits: a Release Eligibility Proof (REP, MQS ≥ 70) and a Premium Quality Proof (PQP, MQS ≥ 85). A Hyperledger Besu QBFT permissioned blockchain with smart contracts provides immutable lifecycle traceability and DID-based access control. In a synthetic data pilot (n = 2000), the system demonstrated engineering feasibility across all five subsystems. These results are engineering pipeline feasibility benchmarks on synthetic data; biological and clinical validation using real MSC data is mandatory follow-on research. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, and endoplasmic reticulum (ER) stress has emerged as an important molecular mechanism underlying myocardial injury and heart failure. This study investigated the expression of the ER stress-related genes GRP78, PERK, and CHOP in peripheral whole blood obtained from patients with acute cardiovascular diseases. A total of 300 participants were enrolled, including 200 patients with ST-segment elevation myocardial infarction (STEMI, n = 55), non-ST-segment elevation myocardial infarction (NSTEMI, n = 88), decompensated heart failure (DHF, n = 40), or unstable angina pectoris (USAP, n = 17), and 100 healthy controls. Relative mRNA expression levels were quantified using quantitative real-time PCR. Intergroup comparisons were performed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Bonferroni adjustment. Significant differences in GRP78, PERK, and CHOP expression were observed among the study groups (all p < 0.001). GRP78 and PERK expression levels were highest in the STEMI and DHF groups, whereas CHOP expression was highest in the STEMI group. Significant positive correlations were identified between troponin and CHOP (r = 0.48), GRP78 (r = 0.42), and PERK (r = 0.39) (all p < 0.001), while weaker but significant associations were observed between inflammatory markers (CRP and NLR) and ER stress-related gene expression. Exploratory receiver operating characteristic (ROC) analysis showed that CHOP demonstrated the highest discriminatory performance for distinguishing patients with acute cardiovascular disease from healthy controls. These findings indicate that peripheral whole-blood ER stress-related gene expression is associated with acute cardiovascular disease and correlates with established biomarkers of myocardial injury and inflammation. Further prospective studies are required to determine the clinical significance of these findings. Full article

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with limited therapeutic options and poor prognosis. The increasing complexity of molecular stratification and treatment selection has stimulated interest in computational and biological modeling approaches for precision oncology. Objective. This narrative review aims to provide a comprehensive overview of digital twins (DTs), DT-enabling computational models, and biological twins (BTs) in CCA, discussing their applications, limitations, and potential integration within hybrid precision medicine frameworks. Methods: A narrative literature review was conducted. To inform the twin-focused sections, a structured PubMed search was performed using predefined keywords related to CCA and twin-related technologies, including organoids, xenografts, organ-on-chip systems. Particular attention was devoted to recent studies addressing computational modeling, patient-derived experimental systems, and translational applications. Results: DT development in CCA is supported by an ecosystem of DT-enabling technologies, including radiomics, artificial intelligence, multi-omics integration, and simulation-based models. However, fully realized medical DTs remain unavailable. BTs, including patient-derived organoids, xenografts, and microfluidic platforms, enable functional validation of therapeutic hypotheses but face challenges related to scalability, standardization, and clinical feasibility. Emerging hybrid DT-BT frameworks seek to combine computational prediction with biological validation through iterative feedback loops, potentially improving patient stratification and treatment personalization. Conclusions: DTs and BTs represent complementary components of an evolving precision oncology ecosystem in CCA. Although technical, biological, regulatory, and implementation challenges remain, the convergence of computational models, longitudinal molecular monitoring, and patient-derived systems may facilitate clinically actionable hybrid twin frameworks. Successful translation will require both technological innovation and healthcare-system improvements to precision medicine access. Full article

Background/Objectives: Persistent atrial fibrillation (AF) is associated with complex structural, electrical, and functional myocardial remodeling that contributes to impaired cardiac performance, symptom burden, and adverse cardiovascular outcomes. Although restoration of sinus rhythm through electrical cardioversion remains a cornerstone of rhythm-control therapy, treatment success is traditionally defined by rhythm maintenance and recurrence rates, while myocardial functional recovery receives substantially less attention. This review aims to summarize current evidence regarding myocardial dysfunction in persistent AF, evaluate available approaches for assessing myocardial recovery after cardioversion, and explore future directions for function-guided rhythm-control strategies. Methods: A narrative review of contemporary literature was performed, focusing on studies published in major cardiovascular journals and current international guidelines. Evidence regarding myocardial remodeling, reverse remodeling after restoration of sinus rhythm, echocardiographic assessment, myocardial strain imaging, biomarker dynamics, and post-cardioversion management strategies was synthesized and critically evaluated. Results: Persistent AF induces multidimensional myocardial dysfunction through tachycardia-mediated injury, structural remodeling, neurohormonal activation, inflammation, and fibrosis. Emerging evidence suggests that restoration of sinus rhythm may initiate a process of reverse remodeling characterized by improvements in left ventricular systolic function, global longitudinal strain, atrial mechanical performance, and biomarker profiles. Advanced echocardiographic techniques and serial biomarker assessment provide valuable opportunities to quantify myocardial recovery beyond conventional rhythm-based endpoints. However, current clinical practice and guideline-directed management remain predominantly focused on rhythm outcomes, while functional recovery is not routinely incorporated into therapeutic decision-making. Based on available evidence, a conceptual framework termed the “Post-Cardioversion Functional Window” is proposed to describe a period of potentially enhanced myocardial recovery during which systematic functional assessment may facilitate individualized management and future risk stratification. Conclusions: Myocardial recovery after restoration of sinus rhythm represents an underrecognized component of contemporary AF management. Integration of echocardiographic, biomarker-based, and clinical functional assessment may improve understanding of post-cardioversion remodeling and support the development of personalized rhythm-control strategies. Future prospective studies are needed to validate myocardial recovery endpoints and determine their role in guiding therapeutic decisions after cardioversion. Full article

Background/objectives: Melatonin has circadian, antioxidant, mitochondrial, and immunomodulatory functions, but human data linking relative melatonergic status to coordinated systemic biomarker burden remain limited. We examined this association and tested its internal robustness to alternative score construction, outlier handling, and missing-data assumptions. Methods: We performed an adult-only cross-sectional secondary analysis of a deidentified biomarker dataset. Of 322 source records, six participants younger than 18 years and two records without age were excluded, yielding 314 adults. Plasma melatonin and 24 h urinary aMT6s were converted to within-cohort rank percentiles and averaged to form a relative melatonergic-axis score. Equal-weight z-score composites represented inflammation, oxidative damage, antioxidant deficit, and biological aging/biological injury; their mean was the integrated systemic biomarker-burden score. Analyses included Kruskal–Wallis tests; Spearman correlations with bootstrap confidence intervals; standardized regression adjusted for age, sex, and BMI; robust covariance estimates; principal component analysis (PCA), winsorization, leave-one-domain/marker-out analyses, and missing-BMI sensitivity models. Results: The lower, intermediate, and higher relative melatonergic tertiles included 105, 104, and 105 adults, respectively. The melatonergic-axis score correlated inversely with integrated systemic burden (Spearman ρ = −0.944; 5000-resample bootstrap 95% CI, −0.953 to −0.931; p < 0.001). In age-, sex-, and BMI-adjusted complete-case models (N = 250), each 1 SD higher axis score was associated with a 0.95 SD lower integrated burden (β = −0.949; HC3 95% CI, −0.983 to −0.915; p < 0.001). Results were similar for separate plasma melatonin and aMT6s models, winsorized composites, a PCA-derived score (PC1 explained 75.5% of marker variance; ρ = −0.947), leave-one-domain/marker-out analyses, and missing-BMI sensitivity models. Conclusions: Lower relative melatonergic status was associated with a highly coordinated adverse systemic biomarker pattern. The exceptional magnitude of the association requires audit of primary assay provenance and independent external replication. Because cancer, microbiome, and liquid biopsy endpoints were not measured, oncology implications remain untested prospective hypotheses. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies. Full article

This comprehensive literature review delves into the multifaceted roles of RNA-binding motif protein 3 (RBM3) in cellular processes, disease pathogenesis, and therapeutic potential. RBM3 has been implicated in shaping cell morphology, synaptic protection in neurodegenerative conditions, and regulating gene expression through binding to specific RNA sequences. In cancer, RBM3 exhibits contrasting effects, influencing cell proliferation, tumorigenic potential, and RNA splicing. Clinical studies suggest RBM3 as a predictive biomarker in chemotherapy response for muscle-invasive bladder cancer. Despite promising therapeutic implications in neuroprotection and cancer, challenges persist in understanding the regulatory mechanisms and clinical behavior of RBM3. Further research is warranted to elucidate the molecular mechanisms underlying RBM3’s diverse functions and its significance as a potential target for personalized medicine in cancer therapy. This review underscores the pivotal role of RBPs, particularly RBM3, in disease progression and highlights the need for continued investigation to harness their therapeutic potential effectively. This review evaluates evidence available through December 2025, with particular emphasis on studies published between 2010 and 2025. Full article

Non-communicable diseases (NCDs), including cancer, cardiovascular, neurodegenerative, autoimmune, and allergic diseases, account for a significant amount of global morbidity and mortality. Chronic viral infections have not been recognized as NCDs, despite the availability of several therapeutic vaccination strategies against oncogenic viruses, such as the hepatitis B virus (HBV) and the human papillomavirus (HPV). Indeed, chronic viral infection leads to the development and progression of malignancies directly linked to the viruses. These considerations support a connection between NCDs, infectious diseases, and therapeutic vaccination. Recent advances in technology have paved the way to the use of vaccines beyond the prevention of infectious diseases, heralding innovative therapeutic and preventative strategies for a variety of chronic NCDs. Here we will review the state of the art of personalized vaccine strategies for NCDs, with an emphasis on the diverse technological platforms used to develop them, including mRNA and DNA vaccines, viral vectors, dendritic cell-based vaccines, nanoparticle delivery systems, and next-generation adjuvants. The review intends to make the case for personalized and antigen-specific vaccination strategies as a compelling option for precision immunotherapy primarily in oncology, where neoantigen-based vaccines are being developed. In addition, we will also review tolerogenic vaccination strategies, vaccination strategies targeting pathological proteins and pathways in neurodegenerative and cardiovascular diseases, and vaccine-based treatment of chronic viral infections. Current evidence about vaccines suggests that several ways are available to induce an immune response or create tolerance to a disease, and possibly altering its course instead of simply controlling the symptoms. However, many challenges are still to be overcome, including disease variability, how to identify appropriate target antigens, the complexity of manufacturing process, long-term safety, and integration with already established treatments. By virtue of the convergence of multiple fields—immunology, genomics, bioinformatics, and new delivery systems—precision vaccinology is gaining momentum. Thus, it is envisaged that personalized vaccines will be an increasingly essential component of future preventive and therapeutic approaches for non-communicable diseases. Full article

Pediatric obesity is a complex, multifactorial pandemic with serious early-onset comorbidities, including prediabetes, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disorders. While lifestyle modifications and the Mediterranean diet remain primary interventions, artificial intelligence (AI) is emerging as a critical tool for early diagnosis and personalized management. This review evaluates the current role of AI in predicting and treating childhood obesity and its complications. A literature search was conducted on PubMed and Google Scholar for English-language articles published from 2015 onward. Search terms included combinations of keywords related to “obesity”, “pediatric”, “comorbidities” (e.g., MASLD, diabetes), and “artificial intelligence” (e.g., machine learning, deep learning, multi-omics). Eligible study types ranged from original articles to systematic reviews and clinical guidelines. By integrating multi-omic data (genome, epigenome, transcriptome, metabolome, microbiota) with socio-psychological metrics, AI can predict obesity risk and early complications. Machine learning (ML) and deep learning have successfully identified specific metabolites, gut flora alterations, neurological pathways, and metabolic SNPs linked to obesity susceptibility. Furthermore, ML-driven prognostic models enable risk assessment for MASLD or diabetes progression, while specialized software supports remote lifestyle monitoring and tailored dietary interventions. AI has the potential to revolutionize pediatric obesity management through precision medicine. However, challenges regarding data privacy, digital literacy, and equitable access persist. Because current evidence relies heavily on limited and heterogeneous pediatric datasets, large-scale, well-characterized, and externally validated cohorts are essential to establish the clinical applicability of AI models before routine implementation. Full article

Campylobacter spp. are common commensals in broiler chickens and certain species are major causes of foodborne illness in humans. However, their on-farm dynamics and environmental dissemination remain poorly understood. This study investigated the occurrence and temporal dynamics of Campylobacter spp. in commercial broiler production systems by integrating faecal and airborne monitoring across three consecutive production cycles in two farms with contrasting productive historical performance. Faecal (n = 24) and air samples (n = 24) were analysed using culture-based methods, quantitative polymerase chain reaction (qPCR), and 16S rRNA gene amplicon sequencing, which were subsequently compared to assess concordance. In faecal samples, Campylobacter spp. colonisation generally occurred from mid-cycle onwards, with earlier and more consistent detection in the farm with suboptimal growth performance. In the optimal growth-performing farm, colonisation was not detected in the first cycle but emerged in subsequent cycles, coinciding with declining productive parameters, which include mortality, average weight at slaughter, Feed Conversion Ratio (FCR), and European Production Efficiency Factor (EPEF). Airborne Campylobacter DNA was intermittently detected by qPCR, in some cases preceding or occurring independently of faecal detection, whereas culture-based methods consistently failed to recover viable Campylobacter from air samples. Microbiome sequencing detected Campylobacter sporadically and at low relative abundances, yielding fewer positive detections across the monitored sampling timepoints than the targeted methods. Overall, qPCR proved to be the most sensitive approach across matrices, while faecal culture provided biologically meaningful data on viable loads. This study also documented temporal changes in Campylobacter detection patterns alongside productive performance indicators under commercial production conditions. These findings highlight the complementary value of faecal and airborne monitoring and underscore the importance of combining targeted molecular and culture-based approaches to characterise Campylobacter dynamics under commercial production conditions. Full article

Background: Patients with atrial fibrillation (AF) and a history of gastrointestinal (GI) bleeding represent a particularly challenging clinical population due to the coexistence of elevated thromboembolic and hemorrhagic risks. Percutaneous left atrial appendage occlusion (LAAO) has emerged as an alternative strategy for stroke prevention in patients in whom long-term oral anticoagulation is contraindicated or poorly tolerated. However, evidence specifically addressing clinical outcomes and optimal postprocedural antithrombotic management in this subgroup remains limited. Methods: A comprehensive systematic literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane CENTRAL from database inception to April 2026. Studies were eligible if they included patients with prior gastrointestinal bleeding as the primary study population or reported separately extractable outcomes for a predefined gastrointestinal bleeding subgroup. The primary outcomes were recurrent GI bleeding, thromboembolic events, and all-cause mortality, while secondary outcomes included procedural success, device-related thrombosis, and postprocedural antithrombotic strategies. Owing to substantial clinical and methodological heterogeneity, findings were synthesized qualitatively in accordance with PRISMA 2020 recommendations. Results: Five observational studies reporting GI bleeding-specific outcomes were included in the systematic evidence synthesis. Procedural success rates were consistently high, and LAAO was associated with acceptable thromboembolic outcomes during follow-up. Nevertheless, recurrent GI bleeding remained a clinically relevant complication, particularly in patients with a prior bleeding history. Postprocedural antithrombotic regimens varied widely, ranging from short-term oral anticoagulation to dual or single antiplatelet therapy and reduced-intensity strategies. Less intensive regimens appeared feasible in carefully selected patients at very high bleeding risk; however, no universally optimal approach could be identified. Conclusions: Available observational evidence suggests that LAAO may represent a stroke prevention option in selected patients with AF and prior GI bleeding, although firm conclusions regarding net clinical benefit and the optimal postprocedural antithrombotic strategy cannot currently be drawn. Its net clinical benefit is closely linked to individualized postprocedural management, particularly the choice and intensity of antithrombotic therapy. These findings highlight the importance of a multidisciplinary, patient-centered approach and underscore the need for prospective studies to establish evidence-based treatment strategies in this high-risk population. Full article