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Search Results (446)

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22 pages, 8947 KB  
Article
Research on Value-Chain-Driven Multi-Level Digital Twin Models for Architectural Heritage
by Guoli Wang, Yaofeng Wang, Ming Guo, Xuanshuo Liang, Yang Fu and Hongda Li
Buildings 2025, 15(17), 2984; https://doi.org/10.3390/buildings15172984 - 22 Aug 2025
Viewed by 170
Abstract
As a national treasure, architectural heritage carries multiple value dimensions such as history, technology, art, and culture. With the increasing demand for architectural heritage protection and utilization, the traditional static digital model of architectural heritage based on geometric expression can no longer meet [...] Read more.
As a national treasure, architectural heritage carries multiple value dimensions such as history, technology, art, and culture. With the increasing demand for architectural heritage protection and utilization, the traditional static digital model of architectural heritage based on geometric expression can no longer meet the practical application of multi-stage and multi-level scenarios. To this end, this paper proposes a value-chain-driven multi-level digital twin model of architectural heritage. Based on the three-stage logic of protection, management, and dissemination of value-chain classification, it integrates four types of models: geometry, physics, rules, and behavior. Combined with different hierarchical application levels, the digital model of architectural heritage is refined into a VCLOD (Value-Chain-Driven Level of Detail) detail hierarchy system to achieve a unified expression from spatial form restoration to intelligent response. Through the empirical application of three typical scenarios: the full-area guided tour of the Forbidden City, the exhibition curation of the central axis and the preventive protection of the Meridian Gate, the model shows the following specific results: (1) the efficiency of tourist guidance is improved through real-time personalized path planning; (2) the exhibition planning and visitor experience are improved through dynamic monitoring and interactive management of the exhibition environment; (3) the predictive analysis and preventive protection measures of structural safety are realized, effectively ensuring the structural safety of the Meridian Gate. The research results provide a theoretical basis and practical support for the systematic expression and intelligent evolution of digital twins of architectural heritage. Full article
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17 pages, 2321 KB  
Article
Variations in the Surface Atmospheric Electric Field on the Qinghai–Tibet Plateau: Observations at China’s Gar Station
by Jia-Nan Peng, Shuai Fu, Yan-Yan Xu, Gang Li, Tao Chen and En-Ming Xu
Atmosphere 2025, 16(8), 976; https://doi.org/10.3390/atmos16080976 - 17 Aug 2025
Viewed by 339
Abstract
The Qinghai-Tibet Plateau, known as the “third pole” of the Earth with an average elevation of approximately 4500 m, offers a unique natural laboratory for probing the dynamic behavior of the global electric circuit. In this study, we conduct a comprehensive analysis of [...] Read more.
The Qinghai-Tibet Plateau, known as the “third pole” of the Earth with an average elevation of approximately 4500 m, offers a unique natural laboratory for probing the dynamic behavior of the global electric circuit. In this study, we conduct a comprehensive analysis of near-surface vertical atmospheric electric field (AEF) measurements collected at the Gar Station (80.1° E, 32.5° N; 4259 m a.s.l.) on the western Tibetan Plateau, spanning the period from November 2021 to December 2024. Fair-weather conditions are imposed. The annual mean AEF at Gar is ∼0.331 kV/m, significantly higher than values observed at lowland and plain sites, indicating a pronounced enhancement in atmospheric electricity associated with high-altitude conditions. Moreover, the AEF exhibits marked seasonal variability, peaking in December (∼0.411–0.559 kV/m) and valleying around July–August (∼0.150–0.242 kV/m), yielding an overall amplitude of approximately 0.3 kV/m. We speculate that this seasonal pattern is primarily driven by variations in aerosol concentration. During winter, increased aerosol loading from residential heating and vehicle emissions due to incomplete combustion reduces atmospheric conductivity by depleting free ions and decreasing ion mobility, thereby enhancing the near-surface AEF. In contrast, lower aerosol concentrations in summer lead to weaker AEF. This seasonal decline in aerosol levels is likely facilitated by stronger winds and more frequent rainfall in summer, which enhance aerosol dispersion and wet scavenging, whereas weaker winds and limited precipitation in winter favor near-surface aerosol accumulation. On diurnal timescales, the Gar AEF curve deviates significantly from the classical Carnegie curve, showing a distinct double-peak and double-trough structure, with maxima at ∼03:00 and 14:00 UT and minima near 00:00 and 10:00 UT. This deviation may partly reflect local influences related to sunrise and sunset. This study presents the longest ground-based AEF observations over the Qinghai–Tibet Plateau, providing a unique reference for future studies on altitude-dependent AEF variations and their coupling with space weather and climate processes. Full article
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20 pages, 4292 KB  
Article
A Novel Method for Analysing the Curvature of the Anterior Lens: Multi-Radial Scheimpflug Imaging and Custom Conic Fitting Algorithm
by María Arcas-Carbonell, Elvira Orduna-Hospital, María Mechó-García, Guisela Fernández-Espinosa and Ana Sanchez-Cano
J. Imaging 2025, 11(8), 257; https://doi.org/10.3390/jimaging11080257 - 1 Aug 2025
Viewed by 279
Abstract
This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) [...] Read more.
This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) change during accommodation and whether these changes are age-dependent. A cross-sectional study was conducted on 104 right eyes from healthy participants aged 21–62 years. Sixteen radial images per eye were acquired using the Galilei Dual Scheimpflug Placido Disk Topographer under four accommodative demands (0, 1, 3, and 5 dioptres (D)). Custom software analysed lens curvature by calculating eccentricity in both meridians. Participants were analysed as a total group and by age subgroups. Accommodative amplitude and monocular accommodative facility were inversely correlated with age. Both PD and ACD significantly decreased with higher accommodative demands and age. Relative eccentricity decreased under accommodation, indicating increased lens curvature, especially in younger participants. Significant curvature changes were detected in the horizontal meridian only, although no statistically significant differences between meridians were found overall. The vertical meridian showed slightly higher eccentricity values, suggesting that it remained less curved. By enabling detailed, meridionally stratified in vivo assessment of anterior lens curvature, this novel method provides a valuable non-invasive approach for characterizing age-related biomechanical changes during accommodation. The resulting insights enhance our understanding of presbyopia progression, particularly regarding the spatial remodelling of the anterior lens surface. Full article
(This article belongs to the Special Issue Current Progress in Medical Image Segmentation)
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19 pages, 3242 KB  
Article
Augmented Reality Navigation for Acupuncture Procedures with Smart Glasses
by Shin-Yan Chiou, Hsiao-Hsiang Chang, Yu-Cheng Chen and Geng-Hao Liu
Electronics 2025, 14(15), 3025; https://doi.org/10.3390/electronics14153025 - 29 Jul 2025
Viewed by 346
Abstract
Traditional acupuncture relies on the precise selection of acupuncture points to adjust Qi flow along meridians. Traditionally, acupuncture points are localized using cun (or body-relative cun) as a proportional measurement. However, locating specific points can be challenging, even for experienced practitioners. This study [...] Read more.
Traditional acupuncture relies on the precise selection of acupuncture points to adjust Qi flow along meridians. Traditionally, acupuncture points are localized using cun (or body-relative cun) as a proportional measurement. However, locating specific points can be challenging, even for experienced practitioners. This study aims to enhance the accuracy and efficiency of acupuncture point localization by introducing an augmented reality (AR) navigation system utilizing AR glasses (Magic Leap One). The system employs a Six-Point Landmark-Based AR Registration method to overlay an acupuncture point model onto a patient’s head without the need for external markers. Methods included testing with traditional Chinese medicine students, measuring positional errors, and evaluating stability. Results demonstrated an average error of 5.01 ± 2.64 mm, which is well within the therapeutic range of 2 cun (about 5 cm), with minimal drift during stability tests. This AR system provides an accurate and intuitive tool for practitioners and learners, reducing variability in acupuncture point selection and offering promise for broader clinical applications. Full article
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11 pages, 1461 KB  
Article
Volumetric Bone Mineral Density Assessed by Dual-Energy CT Predicts Bone Strength Suitability for Cementless Total Knee Arthroplasty
by Dong Hwan Lee, Dai-Soon Kwak, Sheen-Woo Lee, Yong Deok Kim, Nicole Cho and In Jun Koh
Medicina 2025, 61(7), 1305; https://doi.org/10.3390/medicina61071305 - 20 Jul 2025
Viewed by 382
Abstract
Background and Objectives: Adequate bone quality is essential for promoting initial bone ingrowth and preventing early migration during cementless total knee arthroplasty (TKA). However, gold-standard criteria for identifying suitable bone strength have yet to be established. Dual-energy computed tomography (DECT)-based volumetric bone [...] Read more.
Background and Objectives: Adequate bone quality is essential for promoting initial bone ingrowth and preventing early migration during cementless total knee arthroplasty (TKA). However, gold-standard criteria for identifying suitable bone strength have yet to be established. Dual-energy computed tomography (DECT)-based volumetric bone mineral density (vBMD) is an emerging tool for assessing bone quality. This study aimed to determine whether DECT-derived vBMD can accurately predict suitable bone strength for cementless TKA. Materials and Methods: A total of 190 patients undergoing primary TKA with a standardized posterior-stabilized implant were prospectively enrolled. Prior to TKA, DECT-derived vBMD was measured in the femoral box region. Actual bone strength was evaluated using an indentation test on resected femoral box specimens. Correlation and linear regression analyses were performed to assess the relationship between DECT vBMD and actual bone strength. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculations were used to determine the optimal cut-off value and diagnostic accuracy of DECT vBMD in identifying candidates suitable for cementless TKA. Results: DECT-derived vBMD exhibited a strong correlation with actual bone strength (correlation coefficient = 0.719, p < 0.01), while linear regression analysis revealed a moderate association (R2 = 0.51, p < 0.01). In addition, it demonstrated excellent diagnostic performance in predicting adequate bone quality for cementless TKA, yielding an AUC of 0.984, with a sensitivity of 91.9% and a specificity of 92.0%. Conclusions: DECT-derived vBMD is a reliable and accurate tool for assessing bone strength around the knee and predicting the suitable bone quality for cementless TKA. Full article
(This article belongs to the Special Issue Clinical Research in Orthopaedics and Trauma Surgery)
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24 pages, 1808 KB  
Systematic Review
Effectiveness and Safety of Acupuncture for Nausea and Vomiting in Cancer Patients: A Systematic Review and Meta-Analysis
by Sung-A Kim, Sujung Yeo and Sabina Lim
Medicina 2025, 61(7), 1287; https://doi.org/10.3390/medicina61071287 - 17 Jul 2025
Viewed by 1249
Abstract
Background and Objectives: Nausea and vomiting (NV) are common and distressing adverse effects among cancer patients undergoing treatment. Despite the widespread use of pharmacological antiemetics, these medications are often insufficient for controlling nausea and may cause medication interactions and side effects. Acupuncture [...] Read more.
Background and Objectives: Nausea and vomiting (NV) are common and distressing adverse effects among cancer patients undergoing treatment. Despite the widespread use of pharmacological antiemetics, these medications are often insufficient for controlling nausea and may cause medication interactions and side effects. Acupuncture has been proposed as a complementary therapy; however, the comprehensive analysis of its effects on NV across all emetogenic cancer treatments remains limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture in managing NV in cancer patients undergoing chemotherapy, radiotherapy, or surgery. Materials and Methods: We conducted a comprehensive search across three electronic databases and two clinical registry platforms from inception to December 2024. Randomized controlled trials (RCTs) evaluating acupuncture for NV in cancer patients were included. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Safety outcomes were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE). Results: Seventeen RCTs met the inclusion criteria, with twelve studies included in the meta-analysis. Acupuncture did not demonstrate significant effects on acute nausea (RR: 0.98; 95% CI: 0.84–1.15; p = 0.80) or acute vomiting (RR: 0.93; 95% CI: 0.65–1.32; p = 0.67). However, it significantly reduced delayed vomiting (RR: 0.76; 95% CI: 0.61–0.95; p = 0.02). Subgroup analysis demonstrated significant effects when acupuncture was administered for at least five days (RR: 0.56; 95% CI: 0.39–0.81; p = 0.002). The most frequently used acupoints were PC6, ST36, CV12, LI4, LR3, and ST25. No serious adverse events related to acupuncture treatments were reported, with only minor AEs such as localized bleeding and mild bruising observed. Conclusions: Acupuncture represents a safe and effective complementary therapy for managing delayed vomiting in cancer patients receiving emetogenic treatments. Clinicians can anticipate optimal benefits from at least five days of treatment, particularly using acupoints PC6, ST36, CV12, LI4, LR3, and ST25. Further high-quality studies are needed to establish standardized treatment regimens and explore its comprehensive effects on NV. Full article
(This article belongs to the Section Oncology)
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18 pages, 1667 KB  
Article
Multi-Task Deep Learning for Simultaneous Classification and Segmentation of Cancer Pathologies in Diverse Medical Imaging Modalities
by Maryem Rhanoui, Khaoula Alaoui Belghiti and Mounia Mikram
Onco 2025, 5(3), 34; https://doi.org/10.3390/onco5030034 - 11 Jul 2025
Viewed by 883
Abstract
Background: Clinical imaging is an important part of health care providing physicians with great assistance in patients treatment. In fact, segmentation and grading of tumors can help doctors assess the severity of the cancer at an early stage and increase the chances [...] Read more.
Background: Clinical imaging is an important part of health care providing physicians with great assistance in patients treatment. In fact, segmentation and grading of tumors can help doctors assess the severity of the cancer at an early stage and increase the chances of cure. Despite that Deep Learning for cancer diagnosis has achieved clinically acceptable accuracy, there still remains challenging tasks, especially in the context of insufficient labeled data and the subsequent need for expensive computational ressources. Objective: This paper presents a lightweight classification and segmentation deep learning model to assist in the identification of cancerous tumors with high accuracy despite the scarcity of medical data. Methods: We propose a multi-task architecture for classification and segmentation of cancerous tumors in the Brain, Skin, Prostate and lungs. The model is based on the UNet architecture with different pre-trained deep learning models (VGG 16 and MobileNetv2) as a backbone. The multi-task model is validated on relatively small datasets (slightly exceed 1200 images) that are diverse in terms of modalities (IRM, X-Ray, Dermoscopic and Digital Histopathology), number of classes, shapes, and sizes of cancer pathologies using the accuracy and dice coefficient as statistical metrics. Results: Experiments show that the multi-task approach improve the learning efficiency and the prediction accuracy for the segmentation and classification tasks, compared to training the individual models separately. The multi-task architecture reached a classification accuracy of 86%, 90%, 88%, and 87% respectively for Skin Lesion, Brain Tumor, Prostate Cancer and Pneumothorax. For the segmentation tasks we were able to achieve high precisions respectively 95%, 98% for the Skin Lesion and Brain Tumor segmentation and a 99% precise segmentation for both Prostate cancer and Pneumothorax. Proving that the multi-task solution is more efficient than single-task networks. Full article
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23 pages, 1026 KB  
Article
Systemic Factors Fuel Food Insecurity Among Collegiate Student-Athletes: Qualitative Findings from the Running on Empty Study
by Barbara Gordon, Natalie Christensen and Jenifer Reader
Nutrients 2025, 17(14), 2254; https://doi.org/10.3390/nu17142254 - 8 Jul 2025
Viewed by 523
Abstract
Collegiate student-athletes are particularly vulnerable to food insecurity (FI). Prevalence rates range from 9.9% to 65%, although research is limited among this population. Background/Objectives: The challenge of balancing academic and degree progression requirements with training and competition demands can increase the risk for [...] Read more.
Collegiate student-athletes are particularly vulnerable to food insecurity (FI). Prevalence rates range from 9.9% to 65%, although research is limited among this population. Background/Objectives: The challenge of balancing academic and degree progression requirements with training and competition demands can increase the risk for FI among student-athletes. Furthermore, insufficient funds for food has been reported for student-athletes living both on campus and off campus. Methods: This qualitative study employed a phenomenological design and constructivist theoretical framework to explore the experiences of athletic trainers, sports dietitians/nutritionists, and other professionals working with student-athletes in identifying and addressing FI among student-athletes via a series of online focus groups. Results: Participants (n = 27, 12 public colleges) had ≥7 years of collegiate athletics work experience, and most had been in their current position for <3 years. Five approaches to FI screening emerged; specifically, no screening, screening varies by team/sport, informal screening, dietitian screening, and formal screening. Emerging social determinants of FI included financial challenges, competing priorities, cultural/societal impacts, limited life skills, and the food environment. All these factors precipitated on a systems level, including individual, team/athletic department, and university/societal tiers. Conclusions: Athletic department and university policies and budgetary decisions emerged as potential antagonists of food security among student-athletes. FI mitigation strategies for student-athletes must go beyond simply addressing individual factors. Obtainment of food security among collegiate student-athletes requires system changes at the team/athletic department and university tiers. Full article
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15 pages, 1296 KB  
Article
Evolution and Predictors of Right Ventricular Failure in Fontan Patients: A Case-Control Study
by Hannah S. Kim, Ginnie Abarbanell, Kathleen Simpson, Aaron M. Abarbanell, Pirooz Eghtesady, Philip T. Levy and Gautam K. Singh
J. Clin. Med. 2025, 14(13), 4602; https://doi.org/10.3390/jcm14134602 - 29 Jun 2025
Viewed by 441
Abstract
Background: Patients with single right ventricular morphology (SRV) may exhibit impaired function with increased morbidity, mortality, and need for cardiac transplant due to progressive SRV failure after the Fontan procedure. The aim of the study was to longitudinally characterize the cardiac mechanics and [...] Read more.
Background: Patients with single right ventricular morphology (SRV) may exhibit impaired function with increased morbidity, mortality, and need for cardiac transplant due to progressive SRV failure after the Fontan procedure. The aim of the study was to longitudinally characterize the cardiac mechanics and trajectory of disease evolution of SRV failure in Fontan patients. Methods: We performed a case-controlled longitudinal study of 52 patients who underwent extracardiac Fontan palliation for SRV between 1994 and 2015 and compared echocardiographic measures of right ventricular (RV) function, RV-systemic vascular coupling and ventricular remodeling between patients who required heart transplants due to SRV failure (study group, n = 26) and those who did not (control group, n = 26). To define the trajectory, measurements were obtained at four matching time points equivalent in duration from Fontan. Results: RV circumferential shortening function declined in both groups over the time period, but was significantly lower (p < 0.01) in the study group farther from the Fontan. RV-systemic vascular coupling, assessed by systolic time interval measures and RV work, was preserved in the control group, but significantly altered (p < 0.001) in the study group. Relative wall thickness decreased, and the minor/major-axis ratio, as an index of ventricular geometry, increased in the study group, but both remained stable in the control group. Conclusions: This study suggests that positive ventricular remodeling with enhanced circumferential systolic function, and preserved RV-vascular coupling, appear to be adaptive and protective mechanisms against RV failure in Fontan with SRV. These indices of cardiac mechanics may serve as clinically relevant quantifiable markers of disease evolution, and early indicators for therapeutic intervention. Full article
(This article belongs to the Section Cardiology)
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27 pages, 8834 KB  
Article
Genetic and Immunological Profiling of Recent SARS-CoV-2 Omicron Subvariants: Insights into Immune Evasion and Infectivity in Monoinfections and Coinfections
by Nadine Alvarez, Irene Gonzalez-Jimenez, Risha Rasheed, Kira Goldgirsh, Steven Park and David S. Perlin
Viruses 2025, 17(7), 918; https://doi.org/10.3390/v17070918 - 27 Jun 2025
Viewed by 687
Abstract
The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and [...] Read more.
The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and prophylactic interventions. The SARS-CoV-2 variant landscape remains dynamic, with new subvariants continuously emerging, many harboring spike protein mutations linked to immune evasion. In this study, we characterized a panel of live SARS-CoV-2 strains, including those key subvariants implicated in recent waves of infection. Our findings revealed a significant variability in mutation patterns in the spike protein across the strains analyzed. Commercial antibodies and human convalescent plasma (HCoP) samples from unvaccinated donors were ineffective in neutralizing the most recent Omicron subvariants, particularly after the emergence of JN.1 subvariant. Using human airway epithelial cells derived from healthy bronchiolar tissue (hBAEC), we established both monoinfections and coinfections involving SARS-CoV-2, Influenza A virus H1N1 (IFAV_H1N1) and Respiratory Syncytial Virus (RSV). Assessments were conducted to compare viral infectivity and the production and release of immune mediators in the apical and basolateral compartments. Notably, Omicron KP.3.1.1 subvariant induced a more pronounced cytopathic effect in hBAEC compared to its parental strain JN.1 and even surpassed the impact observed with the ancestral wild-type virus (WA1/2020, Washington strain). Furthermore, the coinfection of KP.3.1.1 subvariant with IFAV_H1N1 or RSV did not attenuate SARS-CoV-2 infectivity; instead, it significantly exacerbated the pathogenic synergy in the lung epithelium. Our study demonstrated that pro-inflammatory cytokines IL-6, IFN-β, and IL-10 were upregulated in hBAEC following SARS-CoV-2 monoinfection with recent Omicron subvariants as well as during coinfection with IFAV_H1N1 and RSV. Taken together, our findings offer new insights into the immune evasion strategies and pathogenic potential of evolving SARS-CoV-2 Omicron subvariants, as well as their interactions with other respiratory viruses, carrying important implications for therapeutic development and public health preparedness. Full article
(This article belongs to the Special Issue COVID-19 Complications and Co-infections)
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17 pages, 627 KB  
Review
Major Allele Frequencies in CYP2C9 and CYP2C19 in Asian and European Populations: A Case Study to Disaggregate Data Among Large Racial Categories
by Horng-Ee Vincent Nieh and Youssef Malak Roman
J. Pers. Med. 2025, 15(7), 274; https://doi.org/10.3390/jpm15070274 - 27 Jun 2025
Viewed by 1560
Abstract
CYP2C9 and CYP2C19 are major CYP450 enzymes that heavily influence the hepatic metabolism and bioactivation of many medications, including over-the-counter and narrow therapeutic index drugs. Compared to the wild-type alleles, genetic variants in either gene could potentially alter the pharmacokinetics of widely used [...] Read more.
CYP2C9 and CYP2C19 are major CYP450 enzymes that heavily influence the hepatic metabolism and bioactivation of many medications, including over-the-counter and narrow therapeutic index drugs. Compared to the wild-type alleles, genetic variants in either gene could potentially alter the pharmacokinetics of widely used medications, affect the desired therapeutic outcomes of a drug therapy, or increase the risk of undesired adverse events. The frequency of genetic polymorphisms associated with CYP450 enzymes can widely differ across and between racial and ethnic groups. This narrative review highlights the differences in CYP2C9 and CYP2C19 allele frequencies among European and Asian population subgroups, using published literature. Identifying the substantial differences across European and Asian populations, as well as within Asian subgroups, indicates the need to further scrutinize general population data. Clinical scientists and healthcare providers should advocate for more inclusive clinical pharmacogenomic data and racially and ethnically diverse pharmacogenomic databases. Clinical trials of limited racial and geographical diversity may not necessarily have strong external generalizability for all populations. Furthermore, clinical trials that designate an all-inclusive Asian population consisting of multiple ethnicities may not be adequate due to the perceived genetic differences among Asian subgroups. Gravitating towards a more comprehensive approach to utilizing pharmacogenomic data necessitates granular population-level genetic information which can be leveraged to improve how drug therapies are prescribed, achieve health equity, and advance the future of precision medicine. Full article
(This article belongs to the Special Issue New Trends and Challenges in Pharmacogenomics Research)
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25 pages, 2485 KB  
Article
Epigenetic Changes Regulating Epithelial–Mesenchymal Plasticity in Human Trophoblast Differentiation
by William E. Ackerman IV, Mauricio M. Rigo, Sonia C. DaSilva-Arnold, Catherine Do, Mariam Tariq, Martha Salas, Angelica Castano, Stacy Zamudio, Benjamin Tycko and Nicholas P. Illsley
Cells 2025, 14(13), 970; https://doi.org/10.3390/cells14130970 - 24 Jun 2025
Viewed by 1221
Abstract
The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, [...] Read more.
The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, early onset preeclampsia, and fetal growth restriction. Characterization of the normal differentiation processes is, thus, essential for the analysis of these pathologies. Our gene expression analysis, employing purified human CTB and EVT cells, demonstrates a mechanism similar to the epithelial–mesenchymal transition (EMT), which underlies CTB–EVT differentiation. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. A small subgroup of genes undergoes gains of methylation (GOM), associated with differential gene expression (DE). Prominent in this GOM-DE group are genes involved in epithelial–mesenchymal plasticity (EMP). An exemplar is the transcription factor RUNX1, for which we demonstrate a functional role in regulating the migratory and invasive capacities of trophoblast cells. This analysis highlights epigenetically regulated genes acting to underpin the epithelial–mesenchymal plasticity characteristic of human trophoblast differentiation. Identification of these elements provides important information for the obstetric disorders in which these processes are dysregulated. Full article
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14 pages, 741 KB  
Article
Unsupervised Machine Learning in Identification of Septic Shock Phenotypes and Their In-Hospital Outcomes: A Multicenter Cohort Study
by Song Peng Ang, Jia Ee Chia, Eunseuk Lee, Maria Jose Lorenzo-Capps, Madison Laezzo and Jose Iglesias
J. Clin. Med. 2025, 14(13), 4450; https://doi.org/10.3390/jcm14134450 - 23 Jun 2025
Viewed by 617
Abstract
Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in [...] Read more.
Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in host responses. Aim: To identify discrete subphenotypes of septic shock using admission demographics and laboratory parameters, and to evaluate their relationship with in-hospital outcomes. Methods: We conducted a retrospective multicenter cohort study of 10,462 adult patients with ICD-10-defined septic shock admitted to intensive care units between 2014 and 2015. We used Two-Step Cluster Analysis using log-likelihood distance and the Bayesian Information Criterion to identify two distinct phenotypes. We compared clusters on baseline characteristics, in-hospital outcomes including mortality, days on mechanical ventilation, vasopressor use, acute kidney injury (AKI), AKI requiring renal replacement therapy (RRT), and ICU and hospital lengths of stay. Results: We identified two clusters (Cluster 1, n = 5355 and Cluster 2, n = 5107) in our study. Cluster 1 showed greater biochemical severity at presentation, including higher median lactate (2.40 vs. 2.20 mmol L−1; p < 0.001), serum creatinine (1.39 vs. 1.20 mg dL−1; p < 0.001), blood urea nitrogen (28 vs. 25 mg dL−1; p < 0.001), and neutrophil-to-lymphocyte ratio (11.12 vs. 10.38; p < 0.001), and a higher mean SOFA score (7.05 ± 3.85 vs. 6.76 ± 3.87; p < 0.001). Despite this, Cluster 1 required mechanical ventilation more frequently (46.1% vs. 42.2%; p < 0.001) and had a higher incidence of AKI (58.1% vs. 55.6%; p = 0.009), including more stage 3 AKI (17.2% vs. 15.2%; p < 0.001) and dialysis (6.6% vs. 5.2%; p = 0.005), yet experienced similar in-hospital mortality (15.4% vs. 15.8%; p = 0.615) and comparable ICU (2.18 vs. 2.26 days; p = 0.254) and hospital lengths of stay (6.63 vs. 6.80 days; p = 0.251). Conclusions: Two septic shock phenotypes were identified, one with marked early organ dysfunction (Cluster 1) and another with milder initial derangements (Cluster 2), yet both showed convergent short-term mortality and lengths of stay despite divergent support needs. These results challenge reliance on single-parameter severity markers and underscore the need for phenotype-guided risk stratification and personalized management strategies in septic shock. Full article
(This article belongs to the Section Intensive Care)
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13 pages, 857 KB  
Review
Extracellular Vesicles as Targeted Communicators in Complementary Medical Treatments
by Keehyun Earm, Yung E. Earm and Denis Noble
Int. J. Mol. Sci. 2025, 26(12), 5896; https://doi.org/10.3390/ijms26125896 - 19 Jun 2025
Viewed by 604
Abstract
The supposed meridians of traditional oriental medicine have been a cause of conflict between traditional and modern medical science. A possible resolution has been proposed: That extracellular vesicles, including exosomes, may be the transmitters of traditional therapies such as massage and acupuncture. This [...] Read more.
The supposed meridians of traditional oriental medicine have been a cause of conflict between traditional and modern medical science. A possible resolution has been proposed: That extracellular vesicles, including exosomes, may be the transmitters of traditional therapies such as massage and acupuncture. This article develops that idea by proposing that the pathways between surface and deep structures may be laid down during the embryonic migration of cells from one region of the developing body to distant regions. This hypothesis depends on the proven targeting of vesicular communication via cell surface binding molecules and their complementary binding sites on target cells. The hypothesis is therefore experimentally testable. The article also draws attention to a strong analogy with Charles Darwin’s theory of pangenesis for particulate communication between the soma and germline. Full article
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21 pages, 306 KB  
Review
Individualized Management of Osteoarthritis: The Role of Pharmacogenomics to Optimize Pain Therapy
by Isabella M. Sturgeon and Youssef M. Roman
Future Pharmacol. 2025, 5(2), 30; https://doi.org/10.3390/futurepharmacol5020030 - 13 Jun 2025
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Abstract
Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying [...] Read more.
Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying Antirheumatic Drugs (DMARDs) for OA, current treatment strategies largely focus on symptom relief rather than disease modification. These symptomatic treatments often fail to account for the substantial inter-individual variability in drug response. Pharmacogenomics (PGx), the study of how genetic variation influences drug response, offers a promising approach to personalize OA therapy. This review explores the clinical and pharmacogenomic considerations of commonly used OA medications—acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol—focusing on gene–drug interactions that influence efficacy, safety, and metabolism. Evidence-based recommendations from the Clinical Pharmacogenetics Implementation Consortium guidelines are discussed, where applicable, to highlight actionable genetic variants in very important pharmacogenes such as CYP2D6, CYP2C9, and other important drug-metabolizing encoding genes such as CYP2E1 and UGT1A6. While PGx data are not currently embedded in OA clinical treatment guidelines, their integration into clinical practice may enhance therapeutic outcomes and minimize adverse drug events. This review underscores the potential of PGx as a clinical tool in OA pain management, paving the way toward truly personalized medicine. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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