Search Results (35,230)

Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) remain scarce. This study investigated CPV types present in oral and cutaneous papillomatous lesions in domiciled dogs from Acre and Rondônia States, Brazil. Sixty-one dogs with macroscopically consistent lesions were clinically evaluated, and tissue samples were collected for histopathological examination and PCR targeting the L1 gene. Among these, 37% were histologically diagnosed as squamous papillomas or fibropapillomas, and 49.2% (30/61) tested positive for papillomavirus DNA. Sequencing of the L1 gene revealed that most positive samples belonged to CPV1 (Lambdapapillomavirus 2), while one case was identified as CPV8 (Chipapillomavirus 3). Complete genomes of three CPV1 strains were obtained via high-throughput sequencing and showed high identity with CPV1 strains from other Brazilian regions. Phylogenetic analysis confirmed close genetic relationships among isolates across distinct geographic areas. These findings demonstrate the circulation of genetically conserved CPVs in the Amazon and reinforce the value of molecular and histopathological approaches for the accurate diagnosis and surveillance of viral diseases in domestic dogs, especially in ecologically complex regions. Full article

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Objective: We evaluated the feasibility of a machine-learning (ML) model based on clinical features and radiomics from [¹⁸F]FDG PET/CT images to differentiate between infected and non-infected intracavitary vascular grafts and endografts (iVGEI). Methods: Three ML models were developed: one based on pre-treatment criteria to diagnose a vascular graft infection (“MAGIC-light features”), another using radiomics features from diagnostic [¹⁸F]FDG-PET scans, and a third combining both datasets. The training set included 92 patients (72 iVGEI-positive, 20 iVGEI-negative), and the external test set included 20 iVGEI-positive and 12 iVGEI-negative patients. The abdominal aorta and iliac arteries in the PET/CT scans were automatically segmented using SEQUOIA and TotalSegmentator and manually adjusted, extracting 96 radiomics features. The best-performing models for the MAGIC-light features and PET-radiomics features were selected from 343 unique models. Most relevant features were combined to test three final models using ROC analysis, accuracy, sensitivity, and specificity. Results: The combined model achieved the highest AUC in the test set (mean ± SD: 0.91 ± 0.02) compared with the MAGIC-light-only model (0.85 ± 0.06) and the PET-radiomics model (0.73 ± 0.03). The combined model also achieved a higher accuracy (0.91 vs. 0.82) than the diagnosis based on all the MAGIC criteria and a comparable sensitivity and specificity (0.70 and 1.00 vs. 0.76 and 0.92, respectively) while providing diagnostic information at the initial presentation. The AUC for the combined model was significantly higher than the PET-radiomics model (p = 0.02 in the bootstrap test), while other comparisons were not statistically significant. Conclusions: This study demonstrated the potential of ML models in supporting diagnostic decision making for iVGEI. A combined model using pre-treatment clinical features and PET-radiomics features showed high diagnostic performance and specificity, potentially reducing overtreatment and enhancing patient outcomes. Full article

Background and Objectives: Accurately diagnosing acute appendicitis (AA) in children remains clinically challenging due to overlapping symptoms with other pediatric conditions and limitations in conventional diagnostic tools. The systemic immune-inflammation index (SII) has emerged as a promising biomarker in adult populations; however, its utility in pediatrics is still unclear. This study aimed to evaluate the diagnostic accuracy of SII in distinguishing pediatric acute appendicitis from elective non-inflammatory surgical procedures and to assess its predictive value in identifying complicated cases. Materials and Methods: This retrospective, single-center study included 397 pediatric patients (5–15 years), comprising 297 histopathologically confirmed appendicitis cases and 100 controls. Demographic and laboratory data were recorded at admission. Inflammatory indices including SII, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. ROC curve analysis was performed to evaluate diagnostic performance. Results: SII values were significantly higher in the appendicitis group (median: 2218.4 vs. 356.3; p < 0.001). SII demonstrated excellent diagnostic accuracy for AA (AUROC = 0.95, 95% CI: 0.92–0.97), with 91% sensitivity and 88% specificity at a cut-off > 624. In predicting complicated appendicitis, SII showed moderate discriminative ability (AUROC = 0.66, 95% CI: 0.60–0.73), with 83% sensitivity but limited specificity (43%). Conclusions: SII is a reliable and easily obtainable biomarker for diagnosing pediatric acute appendicitis and may aid in early detection of complicated cases. Its integration into clinical workflows may enhance diagnostic precision, particularly in resource-limited settings. Age-specific validation studies are warranted to confirm its broader applicability. Full article

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10–20% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes. Full article

Shaken Baby Syndrome (SBS) is one of the primary causes of fatal head trauma in infants and young children, occurring in about 33 per 100,000 infants annually in the U.S., with mortality rates being between 15% and 38%. Survivors frequently endure long-term disabilities, such as cognitive deficits, visual impairments, and motor dysfunction. Diagnosing SBS remains difficult due to the lack of visible injuries and delayed symptom onset. Existing detection methods—such as neuroimaging, biomechanical modeling, and infant monitoring systems—cannot perform real-time detection and face ethical, technical, and accuracy limitations. This study proposes an inertial measurement unit (IMU)-based detection system enhanced with machine learning to identify aggressive shaking patterns. Findings indicate that wearable-based motion analysis is a promising method for recognizing high-risk shaking, offering a non-invasive, real-time solution that could minimize infant harm and support timely intervention. Full article

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

 Background/Objectives: Identifying and classifying abnormal lung sounds is essential for diagnosing patients with respiratory disorders. In particular, the simultaneous recording of auscultation signals from multiple clinically relevant positions offers greater diagnostic potential compared to traditional single-channel measurements. This study aims to improve the accuracy of respiratory sound classification by leveraging multichannel signals and capturing positional characteristics from multiple sites in the same patient. Methods: We evaluated the performance of respiratory sound classification using multichannel lung sound data with a deep learning model that combines a convolutional neural network (CNN) and long short-term memory (LSTM), based on mel-frequency cepstral coefficients (MFCCs). We analyzed the impact of the number and placement of channels on classification performance. Results: The results demonstrated that using four-channel recordings improved accuracy, sensitivity, specificity, precision, and F1-score by approximately 1.11, 1.15, 1.05, 1.08, and 1.13 times, respectively, compared to using three, two, or single-channel recordings. Conclusion: This study confirms that multichannel data capture a richer set of features corresponding to various respiratory sound characteristics, leading to significantly improved classification performance. The proposed method holds promise for enhancing sound classification accuracy not only in clinical applications but also in broader domains such as speech and audio processing.  Full article

Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma. Full article

It is believed that caspases may play a significant role in the development of cancer, and the expression levels of genes encoding these proteins may influence the prognosis and clinical course of cancer. Taking into account the information presented, we examined the expression profiles of 11 genes from the caspase family in patients diagnosed with triple-negative breast cancer (TNBC). We qualified 29 patients with TNBC. A fragment of the tumor and a fragment of normal tissue surrounding the tumor were collected from each patient. Then, RNA was isolated, and the reverse transcription process was performed. The expression levels of caspase family genes were determined using the real-time PCR method. The obtained data were correlated with clinical data and compared with data from the Cancer Genome Atlas database using the Breast Cancer Gene Expression Miner v4.8 and Ualcan. Based on the results of the conducted research, it can be assumed that the levels of expression of caspase family genes may be correlated with the clinical course of cancer in patients with TNBC, and further research may indicate that profiling the expression levels of these genes may be used in selecting personalized treatment methods. Full article

Background and Objectives: Depression is a leading cause of disability globally, with treatment challenges including limited access, stigma, and poor adherence. Gamification, which applies game elements such as points, levels, and storytelling into non-game contexts, offers a promising strategy to enhance engagement and augment traditional treatments. Our research is the first study designed to explore the implementation of gamification within the Malaysian context. The objective was to explore the feasibility of implementation of gamification as an adjunctive treatment for adults with depression. Materials and Methods: Focus group discussions were held with five mental health professionals and ten patients diagnosed with moderate depression. The qualitative component assessed perceptions of gamified interventions, while quantitative measures evaluated participants’ depressive and anxiety symptomatology. Results: Three key themes were identified: (1) understanding of gamification as a treatment option, (2) factors influencing its acceptance, and (3) characteristics of a practical and feasible intervention. Clinicians saw potential in gamification to boost motivation, support psychoeducation, and encourage self-paced learning, but they expressed concerns about possible addiction, stigma, and the complexity of gameplay for some patients. Patients spoke of gaming as a source of comfort, escapism, and social connection. Acceptance was shaped by engaging storylines, intuitive design, balanced difficulty, therapist guidance, and clear safety measures. Both groups agreed that gamification should be used in conjunction with standard treatments, be culturally sensitive, and be presented as a meaningful therapeutic approach rather than merely as entertainment. Conclusions: Gamification emerges as an acceptable and feasible supplementary approach for managing depression in Malaysia. Its success depends on culturally sensitive design, robust clinical oversight, and seamless integration with existing care pathways. Future studies should investigate long-term outcomes and establish guidelines for the safe and effective implementation of this approach. We recommend targeted investment into culturally adapted gamified tools, including training, policy development, and collaboration with key stakeholders to realistically implement gamification as a mental health intervention in Malaysia. Full article

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article