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PURPOSE: The extent of honeycombing and reticulation predict the clinical prognosis of IPF. Emphysema, consolidation, and ground glass opacity are visible in HRCT scans. To date, there have been few comprehensive studies that have used these parameters. We conducted automated quantitative analysis to identify predictive parameters for clinical outcomes and then grouped the subjects accordingly. METHODS: CT images were obtained while patients held their breath at full inspiration. Parameters were analyzed using an automated lung texture quantification system. Cluster analysis was conducted on 159 IPF patients and clinical profiles were compared between clusters in terms of survival. RESULTS: Kaplan-Meier analysis revealed that survival rates declined as fibrosis, reticulation, honeycombing, consolidation, and emphysema scores increased. Cox regression analysis revealed that reticulation had the most significant impact on survival rate, followed by honeycombing, consolidation, and emphysema scores. Hierarchical and K-means cluster analyses revealed 3 clusters. Cluster 1 (nâ =â 126) with the lowest values for all parameters had the longest survival duration, and relatively-well preserved FVC and DLCO. Cluster 2 (nâ =â 15) with high reticulation and consolidation scores had the lowest FVC and DLCO values with a predominance of female, while cluster 3 (nâ =â 18) with high honeycombing and emphysema scores predominantly consisted of male smokers. Kaplan-Meier analysis revealed that cluster 2 had the lowest survival rate, followed by cluster 3 and cluster 1. CONCLUSION: Automated quantitative CT analysis provides valuable information for predicting clinical outcomes, and clustering based on these parameters may help identify the high-risk group for management.
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Fibrosis Pulmonar Idiopática , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/mortalidad , Tomografía Computarizada por Rayos X/métodos , Análisis por Conglomerados , Anciano , Persona de Mediana Edad , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Estimación de Kaplan-Meier , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/fisiopatología , Pronóstico , Tasa de Supervivencia , Modelos de Riesgos ProporcionalesRESUMEN
The increasing popularity of pigs has prompted farmers to increase pig production to meet the growing demand. However, while the number of pigs is increasing, that of farm workers has been declining, making it challenging to perform various farm tasks, the most important among them being managing the pigs' health and welfare. This study proposes a pattern mining-based pig behavior analysis system to provide visualized information and behavioral patterns, assisting farmers in effectively monitoring and assessing pigs' health and welfare. The system consists of four modules: (1) data acquisition module for collecting pigs video; (2) detection and tracking module for localizing and uniquely identifying pigs, using tracking information to crop pig images; (3) pig behavior recognition module for recognizing pig behaviors from sequences of cropped images; and (4) pig behavior analysis module for providing visualized information and behavioral patterns to effectively help farmers understand and manage pigs. In the second module, we utilize ByteTrack, which comprises YOLOx as the detector and the BYTE algorithm as the tracker, while MnasNet and LSTM serve as appearance features and temporal information extractors in the third module. The experimental results show that the system achieved a multi-object tracking accuracy of 0.971 for tracking and an F1 score of 0.931 for behavior recognition, while also highlighting the effectiveness of visualization and pattern mining in helping farmers comprehend and manage pigs' health and welfare.
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Algoritmos , Reconocimiento en Psicología , Porcinos , Animales , Granjas , Análisis de SistemasRESUMEN
Genetic variation and epigenetic factors are thought to contribute to the development of hypersensitivity to aspirin. DNA methylation fluctuates dynamically throughout the day. To discover new CpG methylation in lymphocytes associated with aspirin-exacerbated respiratory disease (AERD), we evaluated changes in global CpG methylation profiles from before to after an oral aspirin challenge in patients with AERD and aspirin-tolerant asthma (ATA). Whole-genome CpG methylation levels of peripheral blood mononuclear cells were quantified with an Illumina 860K Infinium Methylation EPIC BeadChip array and then adjusted for inferred lymphocyte fraction (ILF) with GLINT and Tensor Composition Analysis. Among the 866,091 CpGs in the array, differentially methylated CpGs (DMCs) were found in 6 CpGs in samples from all 12 patients with asthma included in the study (AERD, n = 6; ATA, n = 6). DMCs were found in 3 CpGs in the 6 ATA samples and in 615 CpGs in the 6 AERD samples. A total of 663 DMCs in 415 genes and 214 intergenic regions differed significantly in the AERD compared with the ATA. In promoters, 126 CpG loci were predicted to bind to 38 transcription factors (TFs), many of which were factors already known to be involved in the pathogenesis of asthma and immune responses. In conclusion, we identified 615 new CpGs methylated in peripheral blood lymphocytes by oral aspirin challenge in AERD but not in ATA. These findings indicate that oral aspirin challenge induces epigenetic changes in ILFs, specifically in AERD patients, possibly via changes in TF binding, which may have epigenetic effects on the development of AERD.
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Asma Inducida por Aspirina , Asma , Humanos , Aspirina/efectos adversos , Leucocitos Mononucleares/metabolismo , Metilación de ADN , Asma Inducida por Aspirina/genética , Asma Inducida por Aspirina/metabolismo , Asma/genética , Linfocitos/metabolismoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-ß1 (TGF)-ß1 activity and TGF-ß1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-ß1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF.
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Fibrosis Pulmonar Idiopática , Factor de Crecimiento Transformador beta1 , Animales , Humanos , Ratones , Bleomicina , Proteínas de la Matriz Extracelular , Fibrosis , Pulmón/enzimología , Ornitina-Oxo-Ácido Transaminasa , Especies Reactivas de OxígenoRESUMEN
INTRODUCTION: Hand/instrument motion-tracking in surgical simulation provides valuable data to improve psychomotor skills and can serve as a formative evaluation tool. Motion analysis has been well-studied in laparoscopic surgery; however, there are essentially no studies looking at motion-tracking for flexible ureteroscopy (fURS ), a common surgical procedure requiring hand dexterity and 3D spatial awareness. We aimed to design a synchronized motion-tracking and video capture system for fURS capable of collecting objective metrics for use in surgical skills training. METHODS: Motion tracking of the ureteroscope was performed using a motion-tracking platform, inertial measurement units (IMUs), and an optical sensor. Position (x, y, z) and orientation (roll, pitch, yaw) of the ureteroscope handle, lever deflection, and translation of the scope insertion point were collected. Video capture of the operator's hands was collected with a Raspberry Pi camera. All peripherals were controlled on a Raspberry Pi 4 and synchronized to its system clock. RESULTS: Our system demonstrated good accuracy in detecting translation of the ureteroscope in the x- and y-axes, and yaw, pitch and roll of the ureteroscope at discrete orientations of 0, ±30, ±60, and ±90 degrees. Unique to fURS, deflection of the lever was captured by the difference in IMU static accelerations with good accuracy. The optical sensor detected translation of the ureteroscope at the insertion point with good precision and an average error of 5.51%. CONCLUSIONS: We successfully developed a motion-tracking and video-capture system capable of collecting motion-analysis parameters unique to fURS . Future studies will focus on establishing the construct validity of this tool.
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BACKGROUND: Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. METHODS: We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. RESULTS: Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P < 0.001), patients with hypersensitivity pneumonitis (P = 0.043), and patients with nonspecific interstitial pneumonia (P < 0.001). The S100A9 level in BALF of 0.093 ng/mL could distinguish IPF patients from HCs, with a specificity of 78.8% and a sensitivity of 81.6%. Similarly, the S100A9 level in BALF of 0.239 ng/mL had a specificity of 64.7% and a sensitivity of 66.7% for distinguishing IPF patients from patients with other interstitial lung diseases. Additionally, BALF S100A9 levels were significantly correlated with neutrophil counts (r = 0.356, P < 0.001) in BALF. IPF patients with S100A9 levels in BALF > 0.533 ng/mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. CONCLUSION: S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.
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Alveolitis Alérgica Extrínseca , Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Inflamación , Líquido del Lavado Bronquioalveolar , Calgranulina BRESUMEN
Chronic obstructive pulmonary disease (COPD) is a group of illnesses associated with unresolved inflammation in response to toxic environmental stimuli. Persistent exposure to PM is a major risk factor for COPD, but the underlying mechanism remains unclear. Using our established mouse model of PM-induced COPD, we find that repeated PM exposure provokes macrophage-centered chronic inflammation and COPD development. Mechanistically, chronic PM exposure induces transcriptional downregulation of HAAO, KMO, KYNU, and QPRT in macrophages, which are the enzymes of de novo NAD+ synthesis pathway (kynurenine pathway; KP), via elevated chromatin binding of the CCCTC-binding factor (CTCF) near the transcriptional regulatory regions of the enzymes. Subsequent reduction of NAD+ and SIRT1 function increases histone acetylation, resulting in elevated expression of pro-inflammatory genes in PM-exposed macrophages. Activation of SIRT1 by nutraceutical resveratrol mitigated PM-induced chronic inflammation and COPD development. In agreement, increased levels of histone acetylation and decreased expression of KP enzymes were observed in pulmonary macrophages of COPD patients. We newly provide an evidence that dysregulated NAD+ metabolism and consecutive SIRT1 deficiency significantly contribute to the pathological activation of macrophages during PM-mediated COPD pathogenesis. Additionally, targeting PM-induced intertwined metabolic and epigenetic reprogramming in macrophages is an effective strategy for COPD treatment.
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Material Particulado , Enfermedad Pulmonar Obstructiva Crónica , Animales , Ratones , Humanos , Material Particulado/toxicidad , Material Particulado/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuina 1/farmacología , Histonas/metabolismo , NAD/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/genética , Macrófagos , Inflamación/metabolismo , Epigénesis GenéticaRESUMEN
Vascular diseases, such as atherosclerosis and thrombosis, are major causes of morbidity and mortality worldwide. Traditional in vitro models for studying vascular diseases have limitations, as they do not fully recapitulate the complexity of the in vivo microenvironment. Organ-on-a-chip systems have emerged as a promising approach for modeling vascular diseases by incorporating multiple cell types, mechanical and biochemical cues, and fluid flow in a microscale platform. This review provides an overview of recent advancements in engineering organ-on-a-chip systems for modeling vascular diseases, including the use of microfluidic channels, ECM (extracellular matrix) scaffolds, and patient-specific cells. We also discuss the limitations and future perspectives of organ-on-a-chip for modeling vascular diseases.
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Sistemas Microfisiológicos , Enfermedades Vasculares , Humanos , Dispositivos Laboratorio en un Chip , Microfluídica , Matriz Extracelular/metabolismo , Enfermedades Vasculares/terapia , Enfermedades Vasculares/metabolismoRESUMEN
Introduction and Objective: Continuous bladder irrigation (CBI) is used in a variety of clinical settings, including post-transurethral surgery and the emergency department. Currently, CBI administration relies on nurses to diligently monitor and switch irrigation bags, as well as titrate the inflow rate based on effluent color. Inappropriate administration can result in discomfort to patients, clot urinary retention, repeat injury to the pathologic or surgical site, extended hospital stays, and even operative management. Our objective was to create an autonomous CBI system that decreases the incidence of disrupted irrigation flow and monitors the outflow to alert clinicians of critical events. Methods: 3D printing and off-the-shelf microcontrollers were used to design a device to fit the needs identified by stakeholders at our institution. An in vitro model of the bladder was created to test our design. The mechanical, electrical, and software subsystems were adjusted accordingly to meet our design requirements. Results: Our in vitro CBI model was able to simulate routine CBI administration with sudden bleeding. Bovine blood was used to simulate the bleeding events. A device was created that met identified stakeholder needs. Accurate detection of critical bleeding events, catheter blockage, and empty irrigation bags were achieved. The device responds to bleeding appropriately by increasing the irrigation rate. When the catheter is blocked, it stops the irrigation and alerts the nurse. Our system accurately titrated the irrigation rate to match a set outflow blood level parameter, conserving irrigation and minimizing nursing workload. Continuous monitoring of CBI effluent was recorded. Conclusions: We anticipate our device will decrease the cognitive load on nurses in busy clinical settings and improve workflow. Moreover, the detection of critical events will likely decrease patient morbidity. Continuous monitoring of the CBI outflow may prove to be a new clinical decision-making tool for ongoing hematuria. Clinical trial is pending.
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Vejiga Urinaria , Retención Urinaria , Humanos , Animales , Bovinos , Hematuria/etiología , Hemorragia , Irrigación TerapéuticaRESUMEN
Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that erythrocyte membrane protein band 4.1-like 3 (EPB41L3) increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing the EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549) and fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5) by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured using RT-PCR, real-time PCR, and Western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-ß-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of FN1, COL1A1, and VIM. In conclusion, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest the therapeutic potential of EPB41L3 as an anti-fibrotic mediator.
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Fibrosis Pulmonar Idiopática , Factor de Crecimiento Transformador beta1 , Humanos , Factor de Crecimiento Transformador beta1/metabolismo , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Fibroblastos/metabolismo , Transición Epitelial-Mesenquimal/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Cadherinas/metabolismo , Proteínas de Microfilamentos/metabolismoRESUMEN
PURPOSE: A subset of asthmatics suffers from persistent airflow limitation, known as remodeled asthma, despite optimal treatment. Typical quantitative scoring methods to evaluate structural changes of airway remodeling on high-resolution computed tomography (HRCT) are time-consuming and laborious. Thus, easier and simpler methods are required in clinical practice. We evaluated the clinical usefulness of a simple, semi-quantitative method based on 8 HRCT parameters by comparing asthmatics with a persistent decline of post-bronchodilator (BD)-FEV1 to those with a BD-FEV1 that normalized over time and evaluated the relationships of the parameters with BD-FEV1. METHODS: Asthmatics (n = 59) were grouped into 5 trajectories (Trs) according to the changes of BD-FEV1 over 1 year. After 9-12 months of guideline-based treatment, HRCT parameters including emphysema, bronchiectasis, anthracofibrosis, bronchial wall thickening (BWT), fibrotic bands, mosaic attenuation on inspiration, air-trapping on expiration, and centrilobular nodules were classified as present (1) or absent (0) in 6 zones. RESULTS: The Tr5 group (n = 11) was older and exhibited a persistent decline in BD-FEV1. The Tr5 and Tr4 groups (n = 12), who had a lower baseline BD-FEV1 that normalized over time, had longer durations of asthma, frequent exacerbations, and higher doses of steroid use compared to the Tr1-3 groups (n = 36), who had a normal baseline BD-FEV1. The Tr5 group had higher emphysema and BWT scores than the Tr4 (P = 8.25E-04 and P = 0.044, respectively). Scores for the other 6 parameters were not significantly different among the Tr groups. BD-FEV1 was inversely correlated with the emphysema and BWT scores in multivariate analysis (P = 1.70E-04, P = 0.006, respectively). CONCLUSIONS: Emphysema and BWT are associated with airway remodeling in asthmatics. Our simple, semi-quantitative scoring system based on HRCT may be an easy-to-use method for estimating airflow limitation.
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The popularity of dogs has been increasing owing to factors such as the physical and mental health benefits associated with raising them. While owners care about their dogs' health and welfare, it is difficult for them to assess these, and frequent veterinary checkups represent a growing financial burden. In this study, we propose a behavior-based video summarization and visualization system for monitoring a dog's behavioral patterns to help assess its health and welfare. The system proceeds in four modules: (1) a video data collection and preprocessing module; (2) an object detection-based module for retrieving image sequences where the dog is alone and cropping them to reduce background noise; (3) a dog behavior recognition module using two-stream EfficientNetV2 to extract appearance and motion features from the cropped images and their respective optical flow, followed by a long short-term memory (LSTM) model to recognize the dog's behaviors; and (4) a summarization and visualization module to provide effective visual summaries of the dog's location and behavior information to help assess and understand its health and welfare. The experimental results show that the system achieved an average F1 score of 0.955 for behavior recognition, with an execution time allowing real-time processing, while the summarization and visualization results demonstrate how the system can help owners assess and understand their dog's health and welfare.
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Recolección de Datos , Perros , AnimalesRESUMEN
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD), an asthma phenotype, often presents with severe manifestations and it remains widely underdiagnosed because of insufficient awareness of the relationship between the ingestion of nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (ASA), and asthma exacerbation. Our previous genome-wide association study demonstrated an association between a single nucleotide polymorphism (SNP) of the ATP8B3 gene and the risk of AERD. This study examined AERD-related SNPs of the ATP8B3 gene in a large population. METHODS: Twenty-five SNPs of ATP8B3 were genotyped with the GoldenGate assay using VeraCode microbeads in 141 asthmatics with AERD and 995 Aspirin-tolerant asthma (ATA). The genotype distribution was analyzed using logistic regression models. The declines in forced expiratory volume in 1 second (FEV1)following an ASA challenge were compared among the genotypes and haplotypes using a type III generalized linear model. RESULTS: The minor allele frequencies (MAFs) of rs10421558 A>G in the 5'UTR and rs10403288 G>A in the intron were significantly lower in the AERD than the ATA [34.0% vs. 43.8%, OR = 0.66 (0.62-0.92), Pcorr = 0.03 and 28.4% vs. 35.4%, OR = 0.62 (0.59-0.89), Pcorr = 0.016, respectively]. BL1ht5 was significantly higher in the AERD [7.6% vs. 1.6%, OR = 12.23 (0.2-0.51), P = 4.7 × 10 -4 , Pcorr = 0.001]. Among them, rs10421558 A>G and BL1ht5 were associated with the percent decline in FEV1 on the oral ASA challenge test. CONCLUSION: The minor allele of rs10421558 A>G in the 5'UTR may protect against the development of AERD via the increased production of ATP8B3.
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Adenosina Trifosfatasas , Aspirina , Asma Inducida por Aspirina , Regiones no Traducidas 5' , Adenosina Trifosfatasas/genética , Aspirina/efectos adversos , Asma Inducida por Aspirina/genética , Estudio de Asociación del Genoma Completo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND/AIMS: Neutrophilia is frequently observed in bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. Granulocyte colony-stimulating factor (G-CSF) is a potent neutrophil-activating glycoprotein. However, the clinical implications of G-CSF remain poorly understood.in patients with IPF. Therefore, we evaluated the relationship between the G-CSF concentration in BALF and the progression of fibrosis, including in terms of the decline in lung function and long-term survival rate. METHODS: G-CSF concentrations were measured in BALF using enzyme-linked immunosorbent assay (ELISA). The survival rate was estimated using Kaplan-Meier survival analyses. RESULTS: G-CSF protein levels were significantly higher in IPF (n = 87; 1.88 [0 to 5.68 pg/mL]), nonspecific interstitial pneumonia (n = 22; 0.58 [0 to 11.64 pg/mL]), and hypersensitivity pneumonitis (n = 19; 2.48 [0.46 to 5.71 pg/mL]) patients than in normal controls (n = 33; 0 [0 to 0.68 pg/mL]) (all p < 0.01). A receiver operating characteristic curve showed a difference in G-CSF levels between IPF and NC (area under the curve, 0.769): The G-CSF cut-off of 0.96 pg/mL indicated 84.9% specificity and 63.2% sensitivity for IPF. The survival rate was significantly lower in the group with G-CSF > 2.872 pg/mL than in the group with ≤ 2.872 pg/mL (hazard ratio, 2.69; p = 0.041). The annual decline in diffusing capacity of the lung for carbon monoxide was positively correlated with the G-CSF level (p = 0.018). CONCLUSION: G-CSF may participate in the development of IPF and be useful for predicting the prognosis of IPF. Therefore, G-CSF should be analyzed in BALF, in addition to differential cell counts.
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Fibrosis Pulmonar Idiopática , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar , Factor Estimulante de Colonias de Granulocitos , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , PronósticoRESUMEN
BACKGROUND: Significant changes in CpG methylation have been identified in nasal polyps, which are the main targets of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD); however, these polyps are composed of various cellular components. In the present study, whole-genome CpG methylation in peripheral blood lymphocytes (PBLs) was analyzed to define the epigenetic changes in lymphocytes, which are the primary immune cells involved in NERD. MATERIALS AND METHODS: Genomic DNA from peripheral blood mononuclear cells from 27 NERD and 24 aspirin-tolerant asthma (ATA) was subjected to bisulfate conversion and a methylation array. Quantitative CpG methylation, the ß-values as a quantitative measure of DNA methylation, in lymphocytes were calculated after adjustments for cellular composition. RESULTS: Fifty-six hypermethylated and three hypomethylated differentially methylated CpGs (DMCs) in PBLs in the NERD compared with ATA. The top 10 CpG loci predicted the methylation risk score, with a positive predictive value of 91.3%, a negative predictive value of 81.5% and an accuracy of 84.3%. As demonstrated in the nasal polyps, 30 DMCs were predicted to bind to the following 10 transcription factors, ranked in descending order: AP-2alphaA, TFII-1, STAT4, FOXP3, GR, c-Est-1, E2F-1, XBP1, ENKTF-1 and NF-1. Gene ontology analysis identified 13 categories such as regulation of T-helper 17 cell differentiation, including SMAD7 and NFKBIZ. PBLs in NERD contained no DMCs in genes associated with the prostaglandin and leukotriene pathways, which were found in ATA. CONCLUSION: PBLs in NERD form a unique pattern of DNA CpG methylation, and the combined analysis may provide predictive values for NERD.
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Asma , Pólipos Nasales , Antiinflamatorios no Esteroideos/efectos adversos , Islas de CpG/genética , ADN/metabolismo , Metilación de ADN/genética , Humanos , Leucocitos Mononucleares , Linfocitos/metabolismoRESUMEN
Infrared cameras allow non-invasive and 24 h continuous monitoring. Thus, they are widely used in automatic pig monitoring, which is essential to maintain the profitability and sustainability of intensive pig farms. However, in practice, impurities such as insect secretions continuously pollute camera lenses. This causes problems with IR reflections, which can seriously affect pig detection performance. In this study, we propose a noise-robust, real-time pig detection system that can improve accuracy in pig farms where infrared cameras suffer from the IR reflection problem. The system consists of a data collector to collect infrared images, a preprocessor to transform noisy images into clean images, and a detector to detect pigs. The preprocessor embeds a multi-scale spatial attention module in U-net and generative adversarial network (GAN) models, enabling the model to pay more attention to the noisy area. The GAN model was trained on paired sets of clean data and data with simulated noise. It can operate in a real-time and end-to-end manner. Experimental results show that the proposed preprocessor was able to significantly improve the average precision of pig detection from 0.766 to 0.906, with an additional execution time of only 4.8 ms on a PC environment.
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Procesamiento de Imagen Asistido por Computador , Animales , Granjas , Procesamiento de Imagen Asistido por Computador/métodos , PorcinosRESUMEN
Excessive oxidative stress causes lysosomal membrane permeabilization (LMP), which leads to cell death. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into the cytosol and thus maintaining intracellular pH. Previously, we reported that V-ATPase B2 subunit expression is upregulated in the TiO2-exposed lung epithelium. We investigated the role of the lysosomal V-ATPase B2 subunit in oxidative stress-induced alveolar epithelial cell death and in an experimental lung injury/fibrosis model. Overexpression of V-ATPase B2 increased lysosomal pH and lysosomal activities in the cells. In the presence of H2O2, overexpression of V-ATPase B2 increased survival, and silencing of V-ATPase B2 dramatically increased cell death. Overexpression of V-ATPase B2 diminished H2O2-triggered LMP, as evidenced by a reduction in acridine orange staining and leakage of cathepsin D from the lysosome to the cytoplasm. In addition, V-ATPase B2-overexpressing macrophages exhibited significantly enhanced uptake and degradation of collagen. V-ATPase B2-overexpressing transgenic mice showed significant inhibition of the bleomycin-induced increases in lung inflammation and fibrosis. We conclude that V-ATPase B2 is critical for maintaining lysosomal activities against excessive oxidative stress by stabilizing LMP. Our findings reveal a previously unknown role of this V-ATPase subunit in a lung injury and fibrosis model.
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Lesión Pulmonar , Fibrosis Pulmonar , ATPasas de Translocación de Protón Vacuolares/metabolismo , Animales , Colágeno/metabolismo , Fibrosis , Peróxido de Hidrógeno/metabolismo , Lesión Pulmonar/genética , Lesión Pulmonar/metabolismo , Lisosomas/metabolismo , Ratones , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
PURPOSE: Exacerbation of asthma is affected by genetic and environmental factors, but little is known about genetic differences according to smoking status. We evaluated genetic factors associated with asthma exacerbations in smokers and non-smokers, and identified the underlying mechanisms via a genome-wide association study (GWAS) and gene-level analyses according to smoking status. METHODS: A GWAS on the annual frequency of asthma exacerbations was performed in 420 non-smoking and 188 smoking patients with asthma. Gene-wise associations were analyzed by Multi-marker Analysis of GenoMic Annotation (MAGMA); Gene Ontology analysis was also performed. RESULTS: In the non-smoker group, 189 genes showed significant associations with the annual frequency of exacerbations (permutated P < 0.001). The top 10 genes were F5, KLRC1, TAFA2, AIRE, IER3IP1, CHMP2A, IL31RA, ZNF497, DNMT3L, and MYT1L (permutated P = 1.0 × 10-4 - 1.7 × 10-4). In smoking asthmatics, 140 genes-including KANK1, ZMYND12, ZNF34, ANXA11, VAV2, CCDC150, CCDC30, CATSPER3, ARMH2, and MPRIP (permutated P = 9.23 × 10-5 - 5.50 × 10-4)-were associated with asthma exacerbations. Genes participating in the innate immune response in non-smokers and the regulation of cell fate (including apoptosis) in smokers were the major causal genes of asthma exacerbation (FDR q < 0.05). CONCLUSIONS: Our findings not only suggest novel genetic candidates for predicting asthma exacerbations, but also that asthma treatment strategies should take into account smoking behavior.
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Asma , Estudio de Asociación del Genoma Completo , Proteínas Adaptadoras Transductoras de Señales , Asma/genética , Proteínas del Citoesqueleto/genética , Humanos , Canales Iónicos/genética , FumadoresRESUMEN
An increasing number of people own dogs due to the emotional benefits they bring to their owners. However, many owners are forced to leave their dogs at home alone, increasing the risk of developing psychological disorders such as separation anxiety, typically accompanied by complex behavioral symptoms including excessive vocalization and destructive behavior. Hence, this work proposes a multi-level hierarchical early detection system for psychological Separation Anxiety (SA) symptoms detection that automatically monitors home-alone dogs starting from the most fundamental postures, followed by atomic behaviors, and then detecting separation anxiety-related complex behaviors. Stacked Long Short-Term Memory (LSTM) is utilized at the lowest level to recognize postures using time-series data from wearable sensors. Then, the recognized postures are input into a Complex Event Processing (CEP) engine that relies on knowledge rules employing fuzzy logic (Fuzzy-CEP) for atomic behaviors level and higher complex behaviors level identification. The proposed method is evaluated utilizing data collected from eight dogs recruited based on clinical inclusion criteria. The experimental results show that our system achieves approximately an F1-score of 0.86, proving its efficiency in separation anxiety symptomatic complex behavior monitoring of a home-alone dog.
Asunto(s)
Ansiedad de Separación , Conducta Animal , Animales , Ansiedad , Ansiedad de Separación/diagnóstico , Perros , Lógica Difusa , PosturaRESUMEN
BACKGROUND: Toluene diisocyanate (TDI) causes occupational asthma by generating oxidative stress, leading to tissue injury and inflammation. Glutathione transferases (GSTs) are detoxifying enzymes that eliminate oxidative stress. We examined whether the genotypes of the GSTM1 and GSTT1 genes are associated with TDI-induced occupational asthma (TDI-OA). METHODS: The study population consisted of 26 asthmatics with a positive response to the TDI challenge (TDI-PA) and 27 asthmatics with negative responses (TDI-NA). GSTM1 and GSTT1 null and wild-type genotypes were determined using multiplex PCR. The plasma GSTM1 and GSTT1 protein concentrations were determined using ELISA. RESULTS: The GSTM1 null genotype was more frequent in the TDI-PA than in the TDI-NA (77.8 vs. 50.0%, OR = 3.5, p=0.03), while the frequency of the GSTT1 null genotype tended to be higher in the TDI-PA than in the TDI-NA (59.3 vs. 42.3%, OR = 1.98, p=0.21). When analyzed together, the GSTM1/GSTT1 null genotype was more frequent in the TDI-PA than in the TDI-NA (48.2 vs. 15.3%, OR = 6.5, p=0.04). The decline in the FEV in 1 s after TDI challenge was higher with the GSTM1/GSTT1 null than the GSTM1 wild-type/GSTT1 null genotypes (24.29% vs. 7.47%, p=0.02). The plasma GSTM1 level was lower with the GSTM1 null than with the GSTM1 wild-type genotypes both before (13.7 vs. 16.6 ng/mg, p=0.04) and after (12.9 vs. 17.1 ng/mg, p=0.007) the TDI challenge, while the GSTT1 level was not changed with either the GSTT1 null or wild-type genotype. CONCLUSIONS: The GSTM1 null genotype, but not GSTT1 alone, may confer susceptibility to TDI-OA. However, the genetic effect of the GSTM1 null genotype may be enhanced synergistically by the GSTT1 null genotype. The genetic effect of GSTM1 was validated in the plasma as the GSTM1 protein level. Therefore, the GSTM1 and GSTT1 genotypes may be useful diagnostic markers for TDI-OA.