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Brain Sciences Jun 2024This study introduces Multi-Threshold Recurrence Rate Plots (MTRRP), a novel methodology for analyzing dynamic patterns in complex systems, such as those influenced by...
This study introduces Multi-Threshold Recurrence Rate Plots (MTRRP), a novel methodology for analyzing dynamic patterns in complex systems, such as those influenced by neurodegenerative diseases in brain activity. MTRRP characterizes how recurrence rates evolve with increasing recurrence thresholds. A key innovation of our approach, Recurrence Complexity, captures structural complexity by integrating local randomness and global structural features through the product of Recurrence Rate Gradient and Recurrence Hurst, both derived from MTRRP. We applied this technique to resting-state EEG data from patients diagnosed with Alzheimer's Disease (AD), Frontotemporal Dementia (FTD), and age-matched healthy controls. The results revealed significantly higher recurrence complexity in the occipital areas of AD and FTD patients, particularly pronounced in the Alpha and Beta frequency bands. Furthermore, EEG features derived from MTRRP were evaluated using a Support Vector Machine with leave-one-out cross-validation, achieving a classification accuracy of 87.7%. These findings not only underscore the utility of MTRRP in detecting distinct neurophysiological patterns associated with neurodegenerative diseases but also highlight its broader applicability in time series analysis, providing a substantial tool for advancing medical diagnostics and research.
PubMed: 38928565
DOI: 10.3390/brainsci14060565 -
International Journal of Molecular... Jun 2024(, ; CHIKV) is a mosquito-borne global health threat. The main urban vector of CHIKV is the mosquito, which is found throughout Brazil. Therefore, it is important to...
(, ; CHIKV) is a mosquito-borne global health threat. The main urban vector of CHIKV is the mosquito, which is found throughout Brazil. Therefore, it is important to carry out laboratory tests to assist in the virus's diagnosis and surveillance. Most molecular biology methodologies use nucleic acid extraction as the first step and require quality RNA for their execution. In this context, four RNA extraction protocols were evaluated in experimentally infected with CHIKV. Six pools were tested in triplicates (n = 18), each containing 1, 5, 10, 20, 30, or 40 mosquitoes per pool (72 tests). Four commercial kits were compared: QIAamp, Maxwell, PureLink, and PureLink with TRIzol. The QIAamp and PureLink with TRIzol kits had greater sensitivity. Two negative correlations were observed: as the number of mosquitoes per pool increases, the Ct value decreases, with a higher viral load. Significant differences were found when comparing the purity and concentration of RNA. The QIAamp protocol performed better when it came to lower Ct values and higher RNA purity and concentration. These results may provide help in CHIKV entomovirological surveillance planning.
Topics: Chikungunya virus; Aedes; Animals; RNA, Viral; Mosquito Vectors; Chikungunya Fever; Viral Load
PubMed: 38928410
DOI: 10.3390/ijms25126700 -
Cancers Jun 2024High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck...
Development and Validation of Prognostic Models Using Radiomic Features from Pre-Treatment Positron Emission Tomography (PET) Images in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients.
High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck squamous cell carcinoma (HNSCC). Using 124 PET radiomics features and clinical variables (age, sex, stage of cancer, site of cancer) from a cohort of 232 patients, we evaluated four survival models-penalized Cox model, random forest, gradient boosted model and support vector machine-to predict all-cause mortality (ACM), locoregional recurrence/residual disease (LR) and distant metastasis (DM) probability during 36, 24 and 24 months of follow-up, respectively. We developed models with five-fold cross-validation, selected the best-performing model for each outcome based on the concordance index (C-statistic) and the integrated Brier score (IBS) and validated them in an independent cohort of 102 patients. The penalized Cox model demonstrated better performance for ACM (C-statistic = 0.70, IBS = 0.12) and DM (C-statistic = 0.70, IBS = 0.08) while the random forest model displayed better performance for LR (C-statistic = 0.76, IBS = 0.07). We conclude that the ML-based prognostic model can aid clinicians in quantifying prognosis and determining effective treatment strategies, thereby improving favorable outcomes in HNSCC patients.
PubMed: 38927901
DOI: 10.3390/cancers16122195 -
Bioengineering (Basel, Switzerland) Jun 2024Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of excess fat in the liver. If left undiagnosed and untreated during the early stages,...
Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of excess fat in the liver. If left undiagnosed and untreated during the early stages, NAFLD can progress to more severe conditions such as inflammation, liver fibrosis, cirrhosis, and even liver failure. In this study, machine learning techniques were employed to predict NAFLD using affordable and accessible laboratory test data, while the conventional technique hepatic steatosis index (HSI)was calculated for comparison. Six algorithms (random forest, K-nearest Neighbors, Logistic Regression, Support Vector Machine, extreme gradient boosting, decision tree), along with an ensemble model, were utilized for dataset analysis. The objective was to develop a cost-effective tool for enabling early diagnosis, leading to better management of the condition. The issue of imbalanced data was addressed using the Synthetic Minority Oversampling Technique Edited Nearest Neighbors (SMOTEENN). Various evaluation metrics including the F1 score, precision, accuracy, recall, confusion matrix, the mean absolute error (MAE), receiver operating characteristics (ROC), and area under the curve (AUC) were employed to assess the suitability of each technique for disease prediction. Experimental results using the National Health and Nutrition Examination Survey (NHANES) dataset demonstrated that the ensemble model achieved the highest accuracy (0.99) and AUC (1.00) compared to the machine learning techniques that we used and HSI. These findings indicate that the ensemble model holds potential as a beneficial tool for healthcare professionals to predict NAFLD, leveraging accessible and cost-effective laboratory test data.
PubMed: 38927836
DOI: 10.3390/bioengineering11060600 -
Genes Jun 2024Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and... (Observational Study)
Observational Study
BACKGROUND
Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC).
METHODS
This exploratory, observational study integrated radiomic perspectives using computed tomography (CT) and genomic perspectives through next-generation sequencing (NGS) applied to liquid biopsies. Associations between radiomic features and genetic mutations were established using the Area Under the Receiver Operating Characteristic curve (AUC-ROC). Machine learning techniques, including Support Vector Machine (SVM) classification, aim to predict genetic mutations based on radiomic features. The prognostic impact of selected gene variants was assessed using Kaplan-Meier curves and Log-rank tests.
RESULTS
Sixty-six patients underwent screening, with fifty-seven being comprehensively characterized radiomically and genomically. Predominantly males (68.4%), adenocarcinoma was the prevalent histological type (73.7%). Disease staging is distributed across I/II (38.6%), III (31.6%), and IV (29.8%). Significant correlations were identified with mutations of p.Thr145Pro (shape_Sphericity), p.Arg167Gln (glszm_ZoneEntropy, firstorder_TotalEnergy), p.Asp2213Asn (glszm_GrayLevelVariance, firstorder_RootMeanSquared), and p.Asp1529Glu (glcm_Imc1). Patients with the p.Thr145Pro variant demonstrated markedly shorter median survival compared to the wild-type group (9.7 months vs. not reached, = 0.0143; HR: 5.35; 95% CI: 1.39-20.48).
CONCLUSIONS
The exploration of the intersection between radiomics and cancer genetics in NSCLC is not only feasible but also holds the potential to improve genetic predictions and enhance prognostic accuracy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Female; Lung Neoplasms; Middle Aged; High-Throughput Nucleotide Sequencing; Aged; Tomography, X-Ray Computed; Genomics; Mutation; Proto-Oncogene Proteins; Protein-Tyrosine Kinases; Prognosis; Adult; Anaplastic Lymphoma Kinase; Radiomics
PubMed: 38927739
DOI: 10.3390/genes15060803 -
Genes Jun 2024Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic... (Review)
Review
Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases.
Topics: Humans; Diabetic Retinopathy; Genetic Therapy; Macular Degeneration; Genetic Vectors; Dependovirus; Vascular Endothelial Growth Factor A; Animals
PubMed: 38927656
DOI: 10.3390/genes15060720 -
Genes May 2024Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked gene that abrogate reactive oxygen species (ROS)...
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked gene that abrogate reactive oxygen species (ROS) production in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoietic stem and progenitor cells (HSPCs) is a promising technology for therapy for CGD. To support the establishment of efficient and safe gene therapies for CGD, we generated a mouse model harboring a patient-derived mutation in the gene. Our CybbC517del mouse line shows the hallmarks of CGD and provides a source for Cybb-deficient HSPCs that can be used to evaluate gene-therapy approaches in vitro and in vivo. In a setup using Cas9 RNPs and an AAV repair vector in HSPCs, we show that the mutation can be repaired in 19% of treated cells and that treatment restores ROS production by macrophages. In conclusion, our CybbC517del mouse line provides a new platform for refining and evaluating novel gene therapies and studying X-CGD pathophysiology.
Topics: Granulomatous Disease, Chronic; Animals; Genetic Therapy; Mice; CRISPR-Cas Systems; Disease Models, Animal; NADPH Oxidase 2; Reactive Oxygen Species; Hematopoietic Stem Cells; Humans; Macrophages; Mutation
PubMed: 38927642
DOI: 10.3390/genes15060706 -
Biomedicines May 2024Alport syndrome is a hereditary disease caused by mutations in the genes encoding the alpha 3, alpha 4, and alpha 5 chains of type IV collagen. It is characterized by... (Review)
Review
Alport syndrome is a hereditary disease caused by mutations in the genes encoding the alpha 3, alpha 4, and alpha 5 chains of type IV collagen. It is characterized by hematuria, proteinuria, progressive renal dysfunction, hearing loss, and ocular abnormalities. The main network of type IV collagen in the glomerular basement membrane is composed of α3α4α5 heterotrimer. Mutations in these genes can lead to the replacement of this network by an immature network composed of the α1α1α2 heterotrimer. Unfortunately, this immature network is unable to provide normal physical support, resulting in hematuria, proteinuria, and progressive renal dysfunction. Current treatment options for Alport syndrome include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which aim to alleviate glomerular filtration pressure, reduce renal injury, and delay the progression of renal dysfunction. However, the effectiveness of these treatments is limited, highlighting the need for novel therapeutic strategies and medications to improve patient outcomes. Gene therapy, which involves the use of genetic material to prevent or treat diseases, holds promise for the treatment of Alport syndrome. This approach may involve the insertion or deletion of whole genes or gene fragments to restore or disrupt gene function or the editing of endogenous genes to correct genetic mutations and restore functional protein synthesis. Recombinant adeno-associated virus (rAAV) vectors have shown significant progress in kidney gene therapy, with several gene therapy drugs based on these vectors reaching clinical application. Despite the challenges posed by the structural characteristics of the kidney, the development of kidney gene therapy using rAAV vectors is making continuous progress. This article provides a review of the current achievements in gene therapy for Alport syndrome and discusses future research directions in this field.
PubMed: 38927366
DOI: 10.3390/biomedicines12061159 -
Biology Jun 2024is a protozoan tick-borne parasite infecting domestic and wild canids, including foxes, wolves, and jackals. It is mainly found in dogs but has also been detected in...
is a protozoan tick-borne parasite infecting domestic and wild canids, including foxes, wolves, and jackals. It is mainly found in dogs but has also been detected in several wild carnivores, including foxes, wolves, and jackals. Host transmission primarily occurs through the ingestion of infected ticks, typically , with documented instances of transplacental transmission from infected females to cubs. In Serbia, the golden jackal is common throughout the country, and its population has increased in recent years. Previous research has documented the presence of several vector-borne pathogens in the jackal population in Serbia, so we conducted this study to determine the presence, prevalence, and genetic variability of . Over eleven years (2010-2020), 114 animal samples were collected from 23 localities in Serbia. A total of 90/114 (78.95%) jackals were positive for , and they came from 22 localities. Among 15 juveniles, almost half (6/15 (40%)) tested positive for . In addition to the high prevalence, high genetic variability of the pathogen was also found. According to the mutated positions, four sequence types (S4-S7) of were determined. Based on our earlier research on the grey wolf and on this study, it can be observed that various sequence types of circulate within wild canid populations in Serbia. The prevalence of infection in wild carnivores raises significant concerns for wildlife conservation and animal health. Infected animals may act as reservoirs for the disease, posing a potential risk to domestic animals by acting as a source of infection.
PubMed: 38927291
DOI: 10.3390/biology13060411 -
Biomolecules Jun 2024Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that (Nb) infection or its derived products could...
Anti-Inflammatory Responses Produced with -Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model.
Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites with anti-inflammation activity and evaluated the AS-prevention effect. We observed that the metabolite uridine had higher expression levels in mice infected with the Nb and ES (excretory-secretory) products and could be selected as a key metabolite. ES and uridine interventions could reduce the pro-inflammatory responses and increase the anti-inflammatory responses in vitro and in vivo. The apolipoprotein E gene knockout (ApoE) mice were fed with a high-fat diet for the AS modeling. Following the in vivo intervention, ES products or uridine significantly reduced serum and liver lipid levels, alleviated the formation of atherosclerosis, and reduced the pro-inflammatory responses in serum or plaques, while the anti-inflammatory responses showed opposite trends. After blocking with 5-HD (5-hydroxydecanoate sodium) in vitro, the mRNA levels of M2 markers were significantly reduced. When blocked with 5-HD in vivo, the degree of atherosclerosis was worsened, the pro-inflammatory responses were increased compared to the uridine group, while the anti-inflammatory responses decreased accordingly. Uridine, a key metabolite from , showed anti-inflammatory and anti-atherosclerotic effects in vitro and in vivo, which depend on the activation of the mitochondrial ATP-sensitive potassium channel.
Topics: Animals; Mice; Atherosclerosis; Uridine; Anti-Inflammatory Agents; Nippostrongylus; Mice, Knockout; Apolipoproteins E; Disease Models, Animal; KATP Channels; Male; Mitochondria
PubMed: 38927075
DOI: 10.3390/biom14060672