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19 pages, 23946 KiB  
Article
Biomarkers of Inflammation and Radiographic Progression in Axial Spondyloarthritis: A Clinical Evaluation of Leptin, Adiponectin, TNF-α, and IL-17A
by Alexandra-Diana Diaconu, Laurențiu Șorodoc, Cristina Pomîrleanu, Liliana Georgeta Foia, Victorița Șorodoc, Cătălina Lionte, Mara Russu, Vladia Lăpuște, Larisa Ghemiș and Codrina Ancuța
J. Clin. Med. 2025, 14(15), 5605; https://doi.org/10.3390/jcm14155605 (registering DOI) - 7 Aug 2025
Abstract
Background/Objectives: Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disorder affecting the spine and sacroiliac joints, with variable clinical expression. This study assessed serum levels of inflammatory (TNF-α, IL-17A) and metabolic (leptin, adiponectin) biomarkers and their associations with disease activity, inflammation, structural [...] Read more.
Background/Objectives: Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disorder affecting the spine and sacroiliac joints, with variable clinical expression. This study assessed serum levels of inflammatory (TNF-α, IL-17A) and metabolic (leptin, adiponectin) biomarkers and their associations with disease activity, inflammation, structural damage, and comorbidities. Methods: This prospective cross-sectional study assessed 89 axSpA patients using clinical, laboratory, and radiological evaluations. Disease activity was measured using ASDAS-CRP and BASDAI scores. Radiographic damage was quantified using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Serum concentrations of TNF-α, IL-17A, leptin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical and imaging correlations were analyzed. Results: Serum leptin levels correlated significantly with higher disease activity scores, inflammatory markers (CRP, ESR), radiographic progression (syndesmophyte formation, mSASSS), and arterial hypertension. Adiponectin levels were inversely associated with disease activity, structural damage, and arterial hypertension, suggesting anti-inflammatory, bone- and cardio-protective properties. TNF-α levels showed an association with inflammatory markers and were higher in patients with peripheral enthesitis. IL-17A levels were weakly correlated with disease activity and structural severity and were significantly lower in patients with a history of anterior uveitis. Conclusions: Leptin and adiponectin may serve as complementary biomarkers in axSpA, reflecting both inflammatory burden and structural damage. While TNF-α and IL-17A remain key therapeutic targets, their correlation with structural changes appears limited. Biomarker profiling could support personalized disease monitoring. Longitudinal studies are needed to validate prognostic implications. Full article
(This article belongs to the Section Immunology)
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18 pages, 822 KiB  
Systematic Review
Virtual Care Perceptions and Experiences of Older Adults During COVID-19 in Canada: A Systematic Review
by Donna Gao, Angela Xu and Lixia Yang
Healthcare 2025, 13(15), 1937; https://doi.org/10.3390/healthcare13151937 (registering DOI) - 7 Aug 2025
Abstract
Background/Objectives: Older adults (65+) are the fastest growing age group in Canada, comprising 18.8% of the country’s population. During the COVID-19 pandemic, use of virtual care, including telehealth and tele-medicine, increased dramatically among older adults in Canada who often face higher health [...] Read more.
Background/Objectives: Older adults (65+) are the fastest growing age group in Canada, comprising 18.8% of the country’s population. During the COVID-19 pandemic, use of virtual care, including telehealth and tele-medicine, increased dramatically among older adults in Canada who often face higher health risks, mobility limitations, and many barriers to accessing healthcare. Despite the rapid expansion in virtual care, no systematic review has focused specifically on virtual care among older adults in Canada. This review aims to explore the factors influencing virtual care adoption and the experiences of older Canadians during the pandemic through a systematic review. Methods: Conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, the review involved a comprehensive search of PubMed, Scopus, ESCBOHost, and Web of Science on 2 May 2025, yielding 281 unique citations. After screening and applying eligibility criteria, 15 studies employing quantitative, qualitative, or mixed-methods designs, with sample sizes ranging from 15 to 2,282,798, were included and appraised using the Mixed Methods Appraisal Tool (MMAT). Results: The review identified three domains of factors and the ways in which each factor shapes older adults’ virtual care experiences: (1) personal factors influencing virtual care use and demand (e.g., age, education, language, income, immigration status, community sizes), (2) resource factors impacting virtual care adoption (e.g., technology access, support), and (3) varying virtual care experiences among older adults (e.g., in assessment and communication efficacy, privacy, care quality, convenience, safety, and costs). Conclusions: This review highlights the complexities of virtual care engagement among older adults and underscores the need for inclusive, tailored strategies to improve the accessibility and effectiveness of virtual care delivery in both pandemic and post-pandemic contexts. Full article
(This article belongs to the Special Issue Aging and Older Adults’ Healthcare)
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36 pages, 928 KiB  
Review
Reprogramming Atherosclerosis: Precision Drug Delivery, Nanomedicine, and Immune-Targeted Therapies for Cardiovascular Risk Reduction
by Paschalis Karakasis, Panagiotis Theofilis, Panayotis K. Vlachakis, Konstantinos Grigoriou, Dimitrios Patoulias, Antonios P. Antoniadis and Nikolaos Fragakis
Pharmaceutics 2025, 17(8), 1028; https://doi.org/10.3390/pharmaceutics17081028 (registering DOI) - 7 Aug 2025
Abstract
Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery [...] Read more.
Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article
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21 pages, 583 KiB  
Review
Diagnosis and Emerging Biomarkers of Cystic Fibrosis-Related Kidney Disease (CFKD)
by Hayrettin Yavuz, Manish Kumar, Himanshu Ballav Goswami, Uta Erdbrügger, William Thomas Harris, Sladjana Skopelja-Gardner, Martha Graber and Agnieszka Swiatecka-Urban
J. Clin. Med. 2025, 14(15), 5585; https://doi.org/10.3390/jcm14155585 - 7 Aug 2025
Abstract
As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to [...] Read more.
As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to encompass the spectrum of kidney dysfunction observed in this population. Early detection of kidney injury is critical for improving long-term outcomes, yet remains challenging due to the limited sensitivity of conventional laboratory tests, particularly in individuals with altered muscle mass and unique CF pathophysiology. Emerging approaches, including novel blood and urinary biomarkers, urinary extracellular vesicles, and genetic risk profiling, offer promising avenues for identifying subclinical kidney damage. When integrated with machine learning algorithms, these tools may enable the development of personalized risk stratification models and targeted therapeutic strategies. This precision medicine approach has the potential to transform kidney disease management in PwCF, shifting care from reactive treatment of late-stage disease to proactive monitoring and early intervention. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)
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18 pages, 949 KiB  
Article
Caries Experience and Oral Health-Related Habits in Blind and Low-Vision Individuals in Croatia
by Jelena Dumančić, Marijana Radić Vuleta, Božana Lončar Brzak, Ivana Savić Pavičin, Tara Kurpez, Neda Striber and Ivana Čuković-Bagić
J. Clin. Med. 2025, 14(15), 5576; https://doi.org/10.3390/jcm14155576 - 7 Aug 2025
Abstract
Objectives: The aim of the study was to investigate caries experience in correlation with self-reported oral health-related habits in a sample of blind and low-vision individuals in Croatia. Methods: The study is a part of the research in the “Project for [...] Read more.
Objectives: The aim of the study was to investigate caries experience in correlation with self-reported oral health-related habits in a sample of blind and low-vision individuals in Croatia. Methods: The study is a part of the research in the “Project for Oral Health Promotion in Blind and Visually Impaired Persons” conducted at the Zagreb University School of Dental Medicine from 2014 to 2018. The final sample consisted of 85 adults: 42 females and 43 males; 50 blind and 35 low-vision individuals, age range 18–98. The assessment included dental examination and a questionnaire. Results: The median DMFT (Decayed, Missing, and Filled Teeth) index score was 17.0 (IQR = 12.5–22.0), with no significant difference between sexes or between blind and low-vision individuals. The occurrence of untreated caries was low (median D-component = 1.0), while the median F-component was 6.0. There was a significant increase in M-component and DMFT in older age groups. The number of untreated caries (D-component) was significantly correlated with consummation of soft drinks and smoking. Total DMFT did not correlate with frequency of tooth brushing, time since last dental visit, smoking, or level of education. Conclusions: This study revealed high caries experience among blind and visually impaired individuals that did not correlate with factors that normally influence oral health. Similar results were found in the control group, reflecting a 30-year post-war period without organized preventive care. The low number of decayed teeth reflects the availability of public dental care in Croatia; however, preventive care should be provided for both this vulnerable group and the general population. Full article
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25 pages, 1534 KiB  
Review
Recent Advances in Micro- and Nano-Enhanced Intravascular Biosensors for Real-Time Monitoring, Early Disease Diagnosis, and Drug Therapy Monitoring
by Sonia Kudłacik-Kramarczyk, Weronika Kieres, Alicja Przybyłowicz, Celina Ziejewska, Joanna Marczyk and Marcel Krzan
Sensors 2025, 25(15), 4855; https://doi.org/10.3390/s25154855 - 7 Aug 2025
Abstract
Intravascular biosensors have become a crucial and novel class of devices in healthcare, enabling the constant real-time monitoring of essential physiological parameters directly within the circulatory system. Recent developments in micro- and nanotechnology have relevantly improved the sensitivity, miniaturization, and biocompatibility of these [...] Read more.
Intravascular biosensors have become a crucial and novel class of devices in healthcare, enabling the constant real-time monitoring of essential physiological parameters directly within the circulatory system. Recent developments in micro- and nanotechnology have relevantly improved the sensitivity, miniaturization, and biocompatibility of these devices, thereby enabling their application in precision medicine. This review summarizes the latest advances in intravascular biosensor technologies, with a special focus on glucose and oxygen level monitoring, blood pressure and heart rate assessment, and early disease diagnostics, as well as modern approaches to drug therapy monitoring and delivery systems. Key challenges such as long-term biostability, signal accuracy, and regulatory approval processes are critical considerations. Innovative strategies, including biodegradable implants, nanomaterial-functionalized surfaces, and integration with artificial intelligence, are regarded as promising avenues to overcome current limitations. This review provides a comprehensive roadmap for upcoming research and the clinical translation of advanced intravascular biosensors with a strong emphasis on their transformative impact on personalized healthcare. Full article
(This article belongs to the Section Biosensors)
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25 pages, 1054 KiB  
Review
Gut Feeling: Biomarkers and Biosensors’ Potential in Revolutionizing Inflammatory Bowel Disease (IBD) Diagnosis and Prognosis—A Comprehensive Review
by Beatriz Teixeira, Helena M. R. Gonçalves and Paula Martins-Lopes
Biosensors 2025, 15(8), 513; https://doi.org/10.3390/bios15080513 - 7 Aug 2025
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Feature Papers of Biosensors)
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11 pages, 365 KiB  
Review
Precision Oncology in Hodgkin’s Lymphoma: Immunotherapy and Emerging Therapeutic Frontiers
by Adit Singhal, David Mueller, Benjamin Ascherman, Pratik Shah, Wint Yan Aung, Edward Zhou and Maria J. Nieto
Lymphatics 2025, 3(3), 24; https://doi.org/10.3390/lymphatics3030024 - 6 Aug 2025
Abstract
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 [...] Read more.
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
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34 pages, 1345 KiB  
Review
Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections
by Alessandra Pandolfo, Rosalia Paola Gagliardo, Valentina Lazzara, Andrea Perri, Velia Malizia, Giuliana Ferrante, Amelia Licari, Stefania La Grutta and Giusy Daniela Albano
Int. J. Mol. Sci. 2025, 26(15), 7629; https://doi.org/10.3390/ijms26157629 - 6 Aug 2025
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Molecular Research in Airway Diseases)
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45 pages, 4319 KiB  
Review
Advancements in Radiomics-Based AI for Pancreatic Ductal Adenocarcinoma
by Georgios Lekkas, Eleni Vrochidou and George A. Papakostas
Bioengineering 2025, 12(8), 849; https://doi.org/10.3390/bioengineering12080849 - 6 Aug 2025
Abstract
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 [...] Read more.
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
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24 pages, 1028 KiB  
Review
Molecular Links Between Metabolism and Mental Health: Integrative Pathways from GDF15-Mediated Stress Signaling to Brain Energy Homeostasis
by Minju Seo, Seung Yeon Pyeon and Man S. Kim
Int. J. Mol. Sci. 2025, 26(15), 7611; https://doi.org/10.3390/ijms26157611 - 6 Aug 2025
Abstract
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 [...] Read more.
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
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38 pages, 1758 KiB  
Review
Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage
by Charlotte Delrue and Marijn M. Speeckaert
Int. J. Mol. Sci. 2025, 26(15), 7606; https://doi.org/10.3390/ijms26157606 - 6 Aug 2025
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Recent Research on Hypertension and Related Complications)
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18 pages, 1528 KiB  
Review
Sex Differences in Colorectal Cancer: Epidemiology, Risk Factors, and Clinical Outcomes
by Sophia Tsokkou, Ioannis Konstantinidis, Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bangeas, Vasileios Papadopoulos and Alexandros Giakoustidis
J. Clin. Med. 2025, 14(15), 5539; https://doi.org/10.3390/jcm14155539 - 6 Aug 2025
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)
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15 pages, 2070 KiB  
Article
Machine Learning for Personalized Prediction of Electrocardiogram (EKG) Use in Emergency Care
by Hairong Wang and Xingyu Zhang
J. Pers. Med. 2025, 15(8), 358; https://doi.org/10.3390/jpm15080358 - 6 Aug 2025
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Machine Learning in Epidemiology)
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18 pages, 978 KiB  
Review
NUDT15 Pharmacogenetics in Acute Lymphoblastic Leukemia: Synthesizing Progress for Personalized Thiopurine Therapy
by Isfahan Shah Lubis, Kusnandar Anggadiredja, Aluicia Anita Artarini, Nur Melani Sari, Nur Suryawan and Zulfan Zazuli
Med. Sci. 2025, 13(3), 112; https://doi.org/10.3390/medsci13030112 - 5 Aug 2025
Abstract
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 [...] Read more.
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
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