Search Results (137)

Mutations in TP53 inhibit p53 protective behaviors including cell cycle arrest, DNA damage repair protein recruitment, and apoptosis. The ubiquity of p53 in genome-stabilizing functions leads to an aberrant tumor microenvironment in TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Profound immunosuppression mediated by myeloid-derived suppressor cells, the upregulation of cytokines and cell-surface receptors on leukemic cells, the suppression of native immune regulator cells, and metabolic aberrations in the bone marrow are features of the TP53-mutated AML/MDS marrow microenvironment. These localized changes in the bone marrow microenvironment (BMME) explain why traditional therapies for MDS/AML, including chemotherapeutics and hypomethylating agents, are not as effective in TP53-mutated myeloid neoplasms and demonstrate the dire need for new treatments in this patient population. The unique pathophysiology of TP53-mutated disease also provides new therapeutic approaches which are being studied, including intracellular targets (MDM2, p53), cell-surface protein biologics (immune checkpoint inhibitors, BiTE therapy, and antibody–drug conjugates), cell therapies (CAR-T, NK-cell), signal transduction pathways (Hedgehog, Wnt, NF-κB, CCRL2, and HIF-1α), and co-opted biologic pathways (cholesterol synthesis and glycolysis). In this review, we will discuss the pathophysiologic anomalies of the tumor microenvironment in TP53-mutant MDS/AML, the hypothesized mechanisms of chemoresistance it imparts, and how novel therapies are leveraging diverse therapeutic targets to address this critical area of need. Full article

Background/Objectives: Cleft lip and/or palate are common craniofacial anomalies whose surgical repair is classified as clean-contaminated and may be complicated by surgical site infection or palatal fistula. Despite widespread perioperative antibiotic use, there are no standardized, evidence-based recommendations, and rising antimicrobial resistance underlines the need for rational prescribing. This systematic scoping review aimed to map current evidence on prophylactic antibiotic therapy and related perioperative measures in cleft surgery. Methods: A scoping review was conducted using the Arksey and O’Malley framework and reported in line with PRISMA 2020. PubMed, Mendeley and Google Scholar were searched (January 2015–10 February 2025) for English-language retrospective studies, clinical trials, survey studies and systematic reviews concerning prophylactic antibiotics, bone grafting procedures, mouthwash use or oral microbiota in patients undergoing cleft lip and/or palate surgery. Six reviewers independently screened records; two experienced clinicians extracted data on study characteristics, antimicrobial regimens and infectious or microbiological outcomes. Given heterogeneity and the scoping aim, no formal risk-of-bias assessment or meta-analysis was performed. Results: A total of 40 studies met the inclusion criteria, including 21 original research articles. Considerable variation in antibiotic choice, timing and duration was observed, with no clear superiority of any regimen. Single-dose perioperative prophylaxis appeared non-inferior to prolonged courses in several settings. Oral microbiota studies highlighted colonization by resistant and opportunistic pathogens in cleft patients. Conclusions: Current evidence supports individualized, often short-course perioperative antibiotic strategies rather than routine prolonged therapy. High-quality randomized and microbiological studies are required to develop standardized, resistance-conscious guidelines. Full article

Indoor WiFi fingerprint localization often suffers from abnormal fluctuations in received signal strength indicator (RSSI) measurements and from the sensitivity of least-squares support vector machine (LSSVM) hyperparameters to local optima. To address these issues, this paper presents an improved end-to-end localization method that integrates fingerprint reconstruction with adaptive model optimization. First, a knowledge-enhanced anomaly detection and spatial fingerprint repair (KADSFR) model is used to enhance fingerprint database consistency by combining robust Mahalanobis distance, median absolute deviation, and local outlier factor for anomaly detection, followed by weighted k-nearest neighbors interpolation based on composite signal–physical distances. Then, an adaptive particle swarm optimization (APSO) scheme with stagnation detection and spatial exclusion mechanisms is employed to tune the LSSVM regularization coefficient and RBF kernel width under five-fold cross-validation. Experiments show that KADSFR improves fingerprint quality by approximately 10 percent, and the proposed method achieves an average error of 0.74 m, outperforming KNN, WKNN, LSSVM, and APSO-LSSVM by 63.5 percent, 62.8 percent, 34.5 percent, and 16.9 percent, respectively. Sensitivity analysis further confirms strong robustness and stability. Full article

This study addresses the challenge of rapid identification and assessment of localized damage to building envelopes under resource-constrained conditions—specifically, the absence of specialized inspection equipment—with a particular focus on the detrimental effects of such damage on thermal performance and energy efficiency. An efficient detection methodology tailored to small-scale maintenance scenarios is proposed, leveraging the YOLOv11 object detection architecture to develop an intelligent system capable of recognizing common envelope defects in contemporary residential buildings, including cracks, spalling, and sealant failure. The system prioritizes the detection of anomalies that may induce thermal bridging, reduced airtightness, or insulation degradation. Defects are classified according to severity and their potential impact on thermal behavior, enabling a graded, integrated repair strategy that holistically balances structural safety, thermal restoration, and façade aesthetics. By explicitly incorporating energy performance recovery as a core objective, the proposed approach not only enhances the automation of spatial data processing but also actively supports the green operation and low-carbon retrofitting of existing urban building stock. Characterized by low cost, high efficiency, and ease of deployment, this method offers a practical and scalable technical pathway for the intelligent diagnosis of thermal anomalies and the enhancement of building energy performance. It aligns with the principles of high-quality architectural development and sustainable building governance, while concretely advancing operational energy reduction in the built environment and contributing meaningfully to energy conservation goals. Full article

To enhance the overall quality and consistency of depth maps, Digital Surface Models (DSM), and True Digital Orthophoto Map (TDOM) in UAV image reconstruction, this paper proposes a multi-stage adaptive optimization generation method. First, to address the noise and outlier issues in depth maps, an adaptive joint bilateral filtering-based optimization method is introduced. This method repairs anomalous depth values using a four-directional filling strategy, incorporates image-guided joint bilateral filtering to enhance edge structure representation, effectively improving the accuracy and continuity of the depth map. Next, during the DSM generation stage, a method based on depth value voting space and elevation anomaly detection is proposed. A joint mechanism of elevation calculation and anomaly point detection is used to suppress noise and errors, while a height value completion strategy significantly enhances the geometric accuracy and integrity of the DSM. Finally, in the TDOM generation process, occlusion detection and gap-line generation techniques are introduced. Together with uniform lighting, color adjustment, and image gap optimization strategies, this improves texture stitching continuity and brightness consistency, effectively reducing artifacts caused by gaps, blurriness, and lighting differences. Experimental results show that the proposed method significantly improves depth map smoothness, DSM geometric accuracy, and TDOM visual consistency compared to traditional methods, providing a complete and efficient technical pathway for high-quality surface reconstruction. Full article

Background: Neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), intellectual disability (ID), and global developmental delay (GDD), frequently have underlying genetic causes. NCKAP1, a gene essential for actin cytoskeleton remodeling and neuronal development, has recently gained recognition as a promising candidate gene in NDDs. While not yet linked to a defined Mendelian disorder, damaging NCKAP1 variants have been identified in individuals with NDDs. NCKAP1 is also expressed in cardiac tissue, with emerging evidence supporting its potential involvement in cardiac development. Here, we present a case of a patient with neurodevelopmental delay and congenital heart disease (CHD) harboring a novel damaging NCKAP1 variant. Methods: Comprehensive clinical evaluations and trio exome sequencing (proband and parents) were conducted on a patient with complex cardiac and neurodevelopmental phenotypes. Results: We identified a de novo heterozygous frameshift variant in NCKAP1, NM_205842.3:c.2956_2959del p.(Ser986Hisfs*34), predicted to result in loss of function through nonsense-mediated mRNA decay. The patient’s clinical features included neonatally diagnosed and surgically repaired infradiaphragmatic total anomalous pulmonary venous return (TAPVR), intellectual disability, speech delay, and autistic traits. His NDD phenotypes and variant type align well with previously described NCKAP1-associated NDD, while the cardiac anomaly adds evidence to the gene’s expanding phenotypic spectrum. This represents the fourth reported case linking NCKAP1 variants to CHD and/or neurodevelopmental delay. Conclusions: This case strengthens the growing recognition of NCKAP1 in both neurodevelopment and cardiac formation. It highlights the importance of genetic testing for individuals with overlapping developmental and cardiac conditions. Further research is warranted to elucidate the role of NCKAP1 in cardiac development and its contribution to CHD. Full article

Background/Objectives: Systemic sclerosis (SSc) is a rare, complex autoimmune disease characterized by fibrosis of the skin and internal organs. While its pathogenesis is not fully understood, chromosomal instability and telomere attrition have emerged as significant areas of investigation. Methods: This review provides a historical narrative perspective and synthesizes current findings on the role of these genomic anomalies in SSc pathogenesis. We synthesized findings from foundational and recent research articles investigating genotoxic factors, chromosomal aberrations, and telomere biology in SSc. Results: There is a strong historical basis for chromosomal instability in SSc, manifesting as micronuclei, translocations, and breaks. This instability is driven by clastogenic factors and oxidative stress. SSc-specific autoantibodies are implicated; anti-centromere antibodies correlate with aneuploidy and micronuclei, while anti-topoisomerase I may inhibit DNA repair. SSc is also characterized by significant telomere attrition, first reported in 1996 and now confirmed by additional genetic studies. This telomere loss is associated with reduced telomerase activity and the presence of autoantibodies against telomere-associated proteins, including shelterin components. Conclusions: We conclude that inflammation, telomere attrition, and chromosomal instability are linked in a self-perpetuating cycle that drives SSc pathogenesis. We propose that an initial inflammatory stimulus leads to reactive oxygen species production, causing telomere damage and attrition. Critically short telomeres trigger faulty DNA repair mechanisms, such as breakage–fusion–bridge cycles, resulting in chromosomal instability. This genomic damage, in turn, acts as a danger signal, further activating inflammatory pathways and creating a feedback loop that perpetuates fibrosis. Full article

Aortic coarctation (CoA) is a congenital vascular anomaly characterized by luminal narrowing of the aorta, representing approximately 5–8% of all congenital heart defects, and is frequently associated with a bicuspid aortic valve and additional vascular malformations. The clinical spectrum is broad, ranging from severe neonatal heart failure to asymptomatic systemic hypertension in adulthood, with the severity of presentation directly influencing the timing of diagnosis and therapeutic intervention. Over recent decades, management strategies have transitioned from conventional surgical techniques—such as end-to-end anastomosis, subclavian flap aortoplasty, and patch augmentation—to endovascular modalities including balloon angioplasty and stent implantation, with covered stents now constituting the preferred approach in most cases. Nonetheless, late complications remain clinically significant. Post-coarctation aneurysms (pCoAA), particularly following patch aortoplasty, have been reported in up to 50% of patients and necessitate lifelong imaging surveillance. Re-coarctation persists as a therapeutic challenge, especially in neonates, with recurrence risk influenced by anatomical factors and the initial repair method. Optimal outcomes require an individualized, anatomy-tailored approach that judiciously integrates surgical, endovascular, and hybrid techniques. Lifelong surveillance remains essential to mitigate long-term risks, including systemic hypertension, aneurysm formation, and the need for re-intervention. Full article

Municipal sewer networks span across large areas in cities around the world and require regular inspection to identify structural failures, blockages, and other issues that pose public health risks. Traditional inspection methods rely on remote-controlled robotic cameras or CCTV surveys performed by skilled inspectors. These processes are time-consuming, expensive, and often inconsistent; for example, the United States alone has more than 1.2 million miles of underground sewer pipes, and up to 75,000 failures are reported annually. Manual CCTV inspections can only cover a small fraction of the network each year, resulting in delayed discovery of defects and costly repairs. To address these limitations, this paper proposes a scalable and low-power fault detection system that integrates embedded machine vision and Tiny Machine Learning (TinyML) on resource-constrained microcontrollers. The system uses transfer learning to train a lightweight TinyML model for defect classification using a dataset of sewer pipe images and deploys the model on battery-powered devices. Each device captures images inside the pipe, performs on-device inference to detect cracks, intrusions, debris, and other anomalies, and communicates inference results over a long-range LoRa radio link. The experimental results demonstrate that the proposed system achieves 94% detection accuracy with sub-hundred-millisecond inference time and operates for extended periods on battery power. The research contributes a template for autonomous, scalable, and cost-effective sewer condition assessment that can help municipalities prioritize maintenance and prevent catastrophic failures. Full article

Background/Objective: Ventricular septal defect (VSD) is the most common congenital heart anomaly, with the perimembranous subtype (pmVSD) being among the most prevalent forms. Surgical repair remains the gold standard for treatment; however, percutaneous closure has emerged as a promising alternative due to the availability of various occlusion devices. Each technique presents distinct advantages and limitations, particularly in terms of complications and long-term outcomes. We sought to evaluate the safety and mid-term outcomes of pmVSD closure employing the Nit-Occlud^® Le VSD Coil within a single-centre, single-team setting. Methods: Of the 55 patients hospitalised for pmVSD closure, 45 children underwent the procedure with the Nit-Occlud^® Le VSD device. Relevant clinical and defect-related data were collected during hospitalisation and throughout follow-up. Results: Among 45 patients, successful coil implantation was achieved in 41 cases (91.1%). Periprocedural complications occurred in 8 patients (17.8%), including haemolysis, transient atrioventricular block, aortic valve injury, transient ST-segment elevation and supraventricular tachycardia. Two of these complications (4.4%) were classified as severe. The occurrence of complications was significantly associated with the type of VSD shunt (p = 0.03). Conclusions: Transcatheter closure of pmVSD using the Nit-Occlud^® Lê VSD Coil in young children is a feasible and safe option with careful patient selection. Patients with type C pmVSD appear to benefit the most. Nevertheless, potential complications, including haemolysis and aortic valve injury, require close monitoring. Full article

Primary tricuspid regurgitation (TR) is an underrecognized valve disease characterized by structural abnormalities of the tricuspid valve (TV) apparatus, including leaflet prolapse, flail, rheumatic degeneration, carcinoid involvement and congenital malformations such as Ebstein’s anomaly. Historically neglected and often misclassified as functional, primary TR has recently gained attention due to advances in multimodality imaging and increased awareness of its pathophysiological complexity and adverse outcomes. A major challenge that remains is the accurate diagnosis of primary TR, as well as the optimal timing for intervention, particularly in asymptomatic patients. While surgical repair or replacement has been the traditional approach, recent developments in transcatheter therapies, such as tricuspid edge-to-edge repair, have broadened the therapeutic landscape for patients considered at high surgical risk. In this context, personalized medicine has emerged as a central paradigm in the management of this valvular disease. Tailored therapeutic decisions should include anatomical, functional, and clinical parameters, as well as patient-specific risk factors such as age and comorbidities. Advanced imaging modalities, including 3D echocardiography and cardiac magnetic resonance, are essential for guiding this individualized approach. This review summarizes the current understanding of the etiology, pathophysiology, diagnostic tools, and treatment strategies for primary TR, highlighting the critical role of personalized treatment pathways in optimizing clinical outcomes. Full article

Open-pit mining often induces geological hazards such as slope instability, surface subsidence, and ground fissures. To support sustainable mine operations and safety, high-resolution monitoring and mechanism-based interpretation are essential tools for early warning, risk management, and compliant reclamation. This study focuses on the Baorixile open-pit coal mine in Inner Mongolia, China, where 48 Sentinel-1 images acquired between 3 March 2017 and 23 April 2021 were processed using the Small-Baseline Subset and Distributed-Scatterer Interferometric Synthetic Aperture Radar (SBAS-DS-InSAR) technique to obtain dense and reliable time-series deformation. Furthermore, a Trend–Periodic–Residual Subspace-Constrained Regression (TPRSCR) method was developed to decompose the deformation signals into long-term trends, seasonal and annual components, and residual anomalies. By introducing Distributed-Scatterer (DS) phase optimization, the monitoring density in low-coherence regions increased from 1055 to 338,555 points (approximately 321-fold increase). Deformation measurements at common points showed high consistency ($R^2$ = 0.97, regression slope = 0.88; mean rate difference = −0.093 mm/yr, standard deviation = 3.28 mm/yr), confirming the reliability of the results. Two major deformation zones were identified: one linked to ground compaction caused by transportation activities, and the other associated with minor subsidence from pre-mining site preparation. In addition, the deformation field exhibits a superimposed pattern of persistent subsidence and pronounced seasonality. TPRSCR results indicate that long-term trend rates range from −14.03 to 14.22 mm/yr, with a maximum periodic amplitude of 40 mm. Compared with the Seasonal-Trend decomposition using LOESS (STL), TPRSCR effectively suppressed “periodic leakage into trend” and reduced RMSEs of total, trend, and periodic components by 48.96%, 93.33%, and 89.71%, respectively. Correlation analysis with meteorological data revealed that periodic deformation is strongly controlled by precipitation and temperature, with an approximately 34-day lag relative to the temperature cycle. The proposed “monitoring–decomposition–interpretation” framework turns InSAR-derived deformation into sustainability indicators that enhance deformation characterization and guide early warning, targeted upkeep, climate-aware drainage, and reclamation. These metrics reduce downtime and resource-intensive repairs and inform integrated risk management in open-pit mining. Full article

The On-Load Tap Changer (OLTC), as a critical component of transformers, undergoes frequent switching operations that can lead to faults such as contact wear and arc discharge, which are often difficult to detect at an early stage using traditional monitoring methods. In particular, dissolved gas analysis (DGA) in OLTC oil is challenged by the unique oil gas decomposition mechanisms and the presence of background noise, making conventional DGA criteria less effective. Moreover, OLTC oil monitoring data are typically obtained through intermittent sampling, resulting in sparse time series with low resolution that complicate fault prediction. To address these challenges, this paper proposes an integrated framework combining LGOD-based anomaly detection, Locally Weighted Regression (LWR) for data repair, and the ETSformer temporal prediction model. This approach effectively identifies and corrects anomalies, restores the dynamic variation trends of gas concentrations, and enhances prediction accuracy through deep temporal modeling, thereby providing more reliable data support for OLTC state assessment and fault diagnosis. Experimental results demonstrate that the proposed method significantly improves prediction accuracy, enhances sensitivity to gas concentration evolution, and exhibits robust adaptability under both normal and fault scenarios. Furthermore, ablation experiments confirm that the observed performance gains are attributable to the complementary contributions of LGOD, LWR, and ETSformer, rather than any single component alone, highlighting the effectiveness of the integrated approach. Full article

Background and Clinical Significance: Atrial septal defects (ASDs), particularly the ostium secundum type, are congenital cardiac anomalies that can lead to serious complications if left untreated. Percutaneous closure using devices like the Amplatzer Septal Occluder (ASO) has become a widely accepted approach, although complications such as device embolization can occur. Case Presentation: We present a unique case of a 28-year-old woman who developed acute hemodynamic instability and arrhythmias following embolization of an Amplatzer device into the right ventricle during an ASD closure. Despite initial treatment with antiarrhythmic medication, the patient required urgent open-heart surgery for device retrieval and ASD closure. The surgery successfully involved pericardial patch closure of the ASD, device removal from the right ventricle, and the performance of the Kay procedure to address significant tricuspid regurgitation. Postoperative recovery was uneventful, with the patient stabilized and discharged in stable condition. Conclusions: This case highlights the critical need for rapid surgical intervention in cases of device embolization, and the importance of multidisciplinary coordination in managing such complex complications. The combination of ASD closure, device retrieval, and tricuspid valve repair led to a successful outcome, underscoring the importance of timely, decisive action in complex cardiovascular emergencies. Full article

Fanconi anemia (FA) is a genetic disorder characterized by congenital anomalies, bone marrow failure, and cancer predisposition. Among other solid cancers, head and neck squamous cell carcinoma (FA HNSCC) is the most common cancer type in individuals with FA. The FA pathway is required for the complete repair of DNA interstrand crosslinks (ICLs), and unresolved ICLs result in cell cycle arrest, apoptosis, or complex chromosomal rearrangements due to chromosome breaks, ultimately leading to tumorigenesis. FA HNSCCs present earlier (median age of onset in the 30s) and exhibit a more aggressive course with frequent recurrence and second primaries, and entail a poorer survival rate compared to sporadic HNSCC. FA HNSCCs are mostly human papillomavirus (HPV)-negative and frequently carry somatic copy number variations (CNVs), which amplify oncogenes implicated in sporadic HNSCC, but single-nucleotide variants or small insertions and deletions are less frequent than in HPV-negative sporadic HNSCC. A subset of sporadic HNSCC carries pathogenic mutations or promoter methylation in FA genes, which also harbor characteristic somatic CNVs, suggesting shared molecular underpinnings with FA HNSCC. Heightened inflammation from genomic instability and transcriptional activation of retrotransposons contribute to tumorigenesis and increased invasiveness by the epithelial-to-mesenchymal transition. Due to heightened sensitivity to DNA crosslinking agents in patients with FA, platinum-based chemotherapy is generally avoided, which presents a significant hurdle for treatment and thereby leaves limited therapeutic options. Surgical management is the mainstay of therapy if possible, and targeted therapy has been increasingly studied in HNSCC in FA. Full article