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BACKGROUND: Fluid therapy in veterinary medicine is pivotal for treating various conditions in pigs; however, standard solutions, such as Hartmann's solution, may not optimally align with pig physiology. This study explored the development and efficacy of a customized fluid therapy tailored to the ionic concentrations of pig blood, aiming to enhance treatment outcomes and safety in both healthy and diseased pigs. RESULTS: The study involved two experiments: the first to assess the safety and stability of customized fluids in healthy pigs, and the second to evaluate the efficacy in pigs with clinical symptoms of dehydration. In healthy pigs, the administration of customized fluids showed no adverse effects, with slight alterations observed in pO2, hematocrit, and glucose levels in some groups. In symptomatic pigs, the customized fluid group did not show any improvement in clinical symptoms, with no significant changes in blood chemistry or metabolite levels compared to controls. The customized fluid group showed a mild increase in some values after administration, yet within normal physiological ranges. The study reported no significant improvements in clinical or dehydration status, attributing the observed variations in blood test results to the limited sample size and anaesthesia effects rather than fluid characteristics. CONCLUSIONS: Customized fluid therapy, tailored to mimic the ionic concentrations of pig blood, appears to be a safe and potentially more effective alternative to conventional solutions such as Hartmann's solution for treating pigs under various health conditions. Further research with larger sample sizes and controlled conditions is recommended to validate these findings and to explore the full potential of customized fluid therapy in veterinary practice.
Subject(s)
Fluid Therapy , Animals , Fluid Therapy/veterinary , Fluid Therapy/methods , Swine , Dehydration/veterinary , Dehydration/therapy , Female , Swine Diseases/therapy , Male , Hematocrit/veterinaryABSTRACT
The purpose of this study was to evaluate and validate methylene blue migration from printed time-temperature indicators (TTIs) into food. It also highlights the importance of establishing regulatory measures and safety standards for food packaging, suggesting that this can contribute to improving food packaging safety. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to quantify methylene blue migration in various food simulant and food matrix samples. The results show that the level of methylene blue migration varies significantly depending on the chemical properties of the food mimetic and the composition of the food matrix. The established method demonstrated a high sensitivity, with limits of detection (LODs) of 0.0019-0.0706 µg/L (kg) and limits of quantification (LOQs) of 0.0057-0.2138 µg/L (kg). This study highlights the need for a regulatory framework to mitigate the health risks associated with methylene blue in intelligent packaging systems and argues that regulatory thresholds should be set to ensure food safety and quality.
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OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate portal hypertension in patients with decompensated liver cirrhosis. The weekend effect refers to a higher risk of adverse outcomes associated with procedures performed on weekends compared to weekdays. The goal of this study is to determine whether a weekend effect is evident in TIPS procedures. MATERIALS AND METHOD: The study identified patients who underwent TIPS procedures in the NIS database from 2015 to 2020. Patients who were admitted on the weekday or weekends were classified into two cohorts. Preoperative variables, including demographics, comorbidities, primary payer status, and hospital characteristics, were noted. Multivariable analysis was used to assess outcomes. RESULTS: Compared to patients admitted on the weekdays, weekend patients had higher in-hospital mortality (12.87 % vs. 7.96 %, aOR = 1.62, 95 CI 1.32-1.00, p < 0.01), hepatic encephalopathy (33.24 % vs. 26.18 %, aOR = 1.41, 95 CI 1.23-1.63, p < 0.01), acute kidney injury (39.03 % vs. 28.36 %, aOR = 1.68, 95 CI 1.46-1.93, p < 0.01), and transfer out (15.91 % vs. 12.76 %, aOR=1.33, 95 CI 1.11-1.60, p < 0.01). It was also found that weekend patients had longer wait from admission to operation (3.83 ± 0.15 days vs 2.82 ± 0.07 days, p < 0.01), longer LOS (11.22 ± 0.33 days vs 8.38 ± 0.15 days, p < 0.01), and higher total hospital charge (219,973 ± 7,352 dollars vs 172,663 ± 3,183 dollars, p < 0.01). CONCLUSION: Our research unveiled a significant relationship between weekend admission and a higher risk of mortality and morbidity post-TIPS procedure. Eliminating delays in treatment associated with the weekend effect may mitigate this gap to deliver consistent and high-quality care to all patients.
Subject(s)
Hepatic Encephalopathy , Hospital Mortality , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Hepatic Encephalopathy/etiology , Female , Male , Middle Aged , Time Factors , Aged , Retrospective Studies , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Cirrhosis/surgery , Length of Stay/statistics & numerical dataABSTRACT
PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.
Subject(s)
Asthma , Cough , Patient Reported Outcome Measures , Quality of Life , Respiratory Sounds , Severity of Illness Index , Humans , Cough/physiopathology , Cough/psychology , Asthma/complications , Asthma/physiopathology , Asthma/psychology , Female , Male , Middle Aged , Cross-Sectional Studies , Aged , Respiratory Sounds/physiopathology , Adult , Republic of Korea/epidemiology , Registries , Surveys and QuestionnairesABSTRACT
Despite their diverse functions, proteins are inherently constructed from a limited set of building blocks. These compositional constraints pose significant challenges to protein research and its practical applications. Strategically manipulating the cellular protein synthesis system to incorporate novel building blocks has emerged as a critical approach for overcoming these constraints in protein research and application. In the past two decades, the field of genetic code expansion (GCE) has achieved significant advancements, enabling the integration of numerous novel functionalities into proteins across a variety of organisms. This technological evolution has paved the way for the extensive application of genetic code expansion across multiple domains, including protein imaging, the introduction of probes for protein research, analysis of protein-protein interactions, spatiotemporal control of protein function, exploration of proteome changes induced by external stimuli, and the synthesis of proteins endowed with novel functions. In this comprehensive Review, we aim to provide an overview of cellular and biophysical applications that have employed GCE technology over the past two decades.
Subject(s)
Genetic Code , Proteins , Protein Biosynthesis , Protein Engineering/methods , Proteins/genetics , Proteins/metabolism , Proteins/chemistryABSTRACT
RATIONALE AND OBJECTIVES: Interpreting ankle stress radiographs is subjective and time-consuming. We aimed to train an AI model that efficiently screens negative cases, assess the agreement with expert with and without AI-assistance, and compare the workload reduction. MATERIAL AND METHODS: We collected anterior draw test (ADT) and talar tilt test (TTT) ankle stress radiographs from Seoul St. Mary's Hospital and St. Vincent's Hospital. Patients with prior surgery, severe joint fusion, or incomplete images were excluded. Expert measurements of tibio-talar distance (TTD) and tibio-talar angle (TTA) served as reference, defining positive labels as TTD ≥ 8.3 mm or TTA ≥ 6.2°. We trained a VGG16 model on data from hospital A and tested it on three separate test sets (testset1, 2 from St. Mary's Hospital, and testset3 from St. Vincent's Hospital). Three readers (expert, reader2, and the collective reading reports) evaluated the test sets, with and without AI-assistance (focusing only on AI-predicted positive cases). We measured agreement with the expert using Cohen's weighted Kappa and assessed the hypothetical workload reduction. RESULTS: AI-assistance did not significantly affect agreement with the expert for any reader in all test sets. Reader2 showed moderate-substantial agreement for all test sets, while collective reports reached fair agreement. The AI alone demonstrated fair to moderate agreement with the expert. AI-assistance reduced the hypothetical workload by 68.8-89.2% for ADT and 58.3-70.4% for TTT. CONCLUSION: We successfully trained an AI model for ankle stress radiography, achieving an average of 70% workload reduction while maintaining agreement with expert radiologists.
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Background: Immunotherapies using anti-programmed cell death ligand-1 (PD-L1) agents have recently shown remarkable outcomes in patients with non-small cell lung cancer (NSCLC). However, there was a poor correlation between PD-L1 expression and treatment response. Many researchers have focused on the clinicopathological factors associated with prognosis, but the results are conflicting. In the present study, we investigated the clinicopathological significance of PD-L1 overexpression in NSCLC cells. Methods: In total, 344 NSCLC cases with PD-L1 assays were retrospectively analyzed. PD-L1 expression was evaluated via immunohistochemical staining using antibodies against SP263 and SP142. The correlation between clinicopathological factors and PD-L1 expression was analyzed for various clinicopathological features. Results: PD-L1 expression significantly correlated with several poor clinicopathological factors, including the solid component of adenocarcinoma, lymphatic invasion, and recurrence. Squamous cell carcinoma, older age, and male sex were also associated with PD-L1 expression. However, we could not observe correlation between PD-L1 expression and disease-free survival (DFS). A novel finding was that lower metastasis was associated with high PD-L1 expression of SP142 in tumor-infiltrating immune cells (ICs). Conclusions: PD-L1 expression in NSCLC is associated with adverse clinicopathological features and recurrence; therefore, it could be utilized to predict poor prognosis. Furthermore, the high PD-L1 expression of SP142 in tumor-infiltrating ICs could be a potential marker for low metastasis.
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RATIONALE AND OBJECTIVES: MRI reconstruction of undersampled data using a deep learning (DL) network has been recently performed as part of accelerated imaging. Herein, we compared DL-reconstructed T2-weighted image (T2-WI) to conventional T2-WI regarding image quality and degenerative lesion detection. MATERIALS AND METHODS: Sixty-two patients underwent C-spine (n = 27) or L-spine (n = 35) MRIs, including conventional and DL-reconstructed T2-WI. Image quality was assessed with non-uniformity measurement and 4-scale grading of structural visibility. Three readers (R1, R2, R3) independently assessed the presence and types of degenerative lesions. Student t-test was used to compare non-uniformity measurements. Interprotocol and interobserver agreement of structural visibility was analyzed with Wilcoxon signed-rank test and weighted-κ values, respectively. The diagnostic equivalence of degenerative lesion detection between two protocols was assessed with interchangeability test. RESULTS: The acquisition time of DL-reconstructed images was reduced to about 21-58% compared to conventional images. Non-uniformity measurement was insignificantly different between the two images (p-value = 0.17). All readers rated DL-reconstructed images as showing the same or superior structural visibility compared to conventional images. Significantly improved visibility was observed at disk margin of C-spine (R1, p < 0.001; R2, p = 0.04) and dorsal root ganglia (R1, p = 0.03; R3, p = 0.02) and facet joint (R1, p = 0.04; R2, p < 0.001; R3, p = 0.03) of L-spine. Interobserver agreements of image quality were variable in each structure. Clinical interchangeability between two protocols for degenerative lesion detection was verified showing <5% in the upper bounds of 95% confidence intervals of agreement rate differences. CONCLUSIONS: DL-reconstructed T2-WI demonstrates comparable image quality and diagnostic performance with conventional T2-WI in spine imaging, with reduced acquisition time.
Subject(s)
Deep Learning , Humans , Magnetic Resonance Imaging/methodsABSTRACT
PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.
Subject(s)
Antitussive Agents , Codeine , Humans , Codeine/therapeutic use , Antitussive Agents/therapeutic use , Prospective Studies , Chronic Cough , Cohort Studies , Cough/drug therapy , Cough/etiologyABSTRACT
Mood disorders, particularly major depressive disorder (MDD) and bipolar disorder (BD), are often underdiagnosed, leading to substantial morbidity. Harnessing the potential of emerging methodologies, we propose a novel multimodal fusion approach that integrates patient-oriented brain structural magnetic resonance imaging (sMRI) scans with DNA whole-exome sequencing (WES) data. Multimodal data fusion aims to improve the detection of mood disorders by employing established deep-learning architectures for computer vision and machine-learning strategies. We analyzed brain imaging genetic data of 321 East Asian individuals, including 147 patients with MDD, 78 patients with BD, and 96 healthy controls. We developed and evaluated six fusion models by leveraging common computer vision models in image classification: Vision Transformer (ViT), Inception-V3, and ResNet50, in conjunction with advanced machine-learning techniques (XGBoost and LightGBM) known for high-dimensional data analysis. Model validation was performed using a 10-fold cross-validation. Our ViT â XGBoost fusion model with MRI scans, genomic Single Nucleotide polymorphism (SNP) data, and unweighted polygenic risk score (PRS) outperformed baseline models, achieving an incremental area under the curve (AUC) of 0.2162 (32.03% increase) and 0.0675 (+8.19%) and incremental accuracy of 0.1455 (+25.14%) and 0.0849 (+13.28%) compared to SNP-only and image-only baseline models, respectively. Our findings highlight the opportunity to refine mood disorder diagnostics by demonstrating the transformative potential of integrating diverse, yet complementary, data modalities and methodologies.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Humans , Mood Disorders/diagnostic imaging , Mood Disorders/genetics , Mood Disorders/pathology , Depressive Disorder, Major/genetics , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/genetics , Brain/pathology , Neuroimaging/methods , Magnetic Resonance Imaging/methodsABSTRACT
Chemically modified proteins have diverse applications; however, conventional chemo-selective methods often yield heterogeneously labeled products. To address this limitation, site-specific protein labeling holds significant potential, driving extensive research in this area. Nevertheless, site-specific modification of native proteins remains challenging owing to the complexity of their functional groups. Therefore, a method for site-selective labeling of intact proteins is aimed to design. In this study, a novel approach to traceless affinity-directed intact protein labeling is established, which leverages small binding proteins and genetic code expansion technology. By applying this method, a site-specific antibody labeling with a drug, which leads to the production of highly effective antibody-drug conjugates specifically targeting breast cancer cell lines is achieved. This approach enables traceless conjugation of intact target proteins, which is a critical advantage in pharmaceutical applications. Furthermore, small helical binding proteins can be easily engineered for various target proteins, thereby expanding their potential applications in diverse fields. This innovative approach represents a significant advancement in site-specific modification of native proteins, including antibodies. It also bears immense potential for facilitating the development of therapeutic agents for various diseases.
Subject(s)
Immunoconjugates , Proteins/metabolism , AntibodiesABSTRACT
RATIONALE AND OBJECTIVES: The purpose of this study was to verify the feasibility of magnetic resonance fingerprinting (MRF)-derived synovial fluid fraction (SFF) mapping for quantifying subvoxel-sized cartilage defects. MATERIALS AND METHODS: MRF was performed on a 3-Tesla scanner and used to derive T2 and SFF maps. An ex vivo experiment was performed using bovine bone; different numbers of holes (4, 6, 8, 10, and 12) were drilled separately on the articular surface, and SFF values were compared among the drilled areas. In a clinical study, 16 osteoarthritis patients underwent sagittal 3D fast spinecho (FSE) and MRF scanning, and knee cartilage segmentation was performed on each image. For morphologic analysis, fluid-excluded images of the SFF (FEISFF) and T2 maps (FEIT2) were generated using the cartilage segmentations, and the whole-organ magnetic resonance imaging score (WORMS) of each FEI and 3D FSE image were compared using the kappa coefficient. For quantitative analysis, intact cartilage volumes in the SFF (VSFF) and T2 maps (VT2) were calculated, and their correlations with reference to the actual cartilage volume on 3D FSE images (V3D) were evaluated. RESULTS: In the ex vivo experiment, the SFF value increased as the number of holes increased. The kappa coefficients of the WORMS were 0.80 and 0.64 in the SFF and T2 maps, respectively, and substantial to almost perfect agreement was observed in the medial tibiofemoral joint. The V3D-VSFF and V3D-VT2 correlation coefficients differed by 0.03 or more in the medial tibiofemoral joint. CONCLUSION: The MRF-derived SFF map can feasibly evaluate small, invisible cartilage defects and quantify cartilage volumes.
Subject(s)
Cartilage Diseases , Cartilage, Articular , Humans , Animals , Cattle , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Synovial Fluid/diagnostic imaging , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Cartilage Diseases/pathology , Magnetic Resonance SpectroscopyABSTRACT
Ellagic acid (EA) is a natural polyphenol and a free radical scavenger with antioxidant properties. This study investigated the protective effects of EA during in vitro maturation (IVM) of porcine oocytes. To determine the optimal concentration, IVM medium was supplemented with various concentrations of EA. Treatment with 10 µM EA (10 EA) resulted in the highest cleavage rate, blastocyst formation rate, and total cell number per blastocyst and the lowest percentage of apoptotic cell in parthenogenetic blastocysts. In the 10 EA group, abnormal spindle and chromosome misalignment were rescued and the ratio of phosphorylated p44/42 to total p44/42 was increased. Furthermore, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, and antioxidant genes (Nrf2, HO-1, CAT, and SOD1) were significantly upregulated in the 10 EA group. mRNA expression of developmental-related (CDX2, POU5F1, and SOX2) and anti-apoptotic (BCL2L1) genes was significantly upregulated in the 10 EA group, while mRNA expression of pro-apoptotic genes (BAK, FAS, and CASP3) was significantly downregulated. Ultimately, following somatic cell nuclear transfer, the blastocyst formation rate was significantly increased and the percentage of apoptotic cell in blastocysts was significantly decreased in the 10 EA group. In conclusion, addition of 10 EA to IVM medium improved oocyte maturation and the subsequent embryo development capacity through antioxidant mechanisms. These findings suggest that EA can enhance the efficiencies of assisted reproductive technologies.
Subject(s)
Antioxidants , Ellagic Acid , Swine , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Ellagic Acid/pharmacology , Ellagic Acid/metabolism , In Vitro Oocyte Maturation Techniques/veterinary , In Vitro Oocyte Maturation Techniques/methods , Oocytes/physiology , Parthenogenesis , Embryonic Development , Blastocyst/physiology , Reactive Oxygen Species/metabolism , RNA, Messenger/metabolismABSTRACT
PURPOSE: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI). METHOD: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm2) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI. RESULTS: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89]). CONCLUSIONS: DL reconstruction can improve the image quality of whole-spine diffusion imaging.
Subject(s)
Deep Learning , Female , Humans , Middle Aged , Retrospective Studies , Diffusion Magnetic Resonance Imaging/methods , Echo-Planar Imaging/methods , Spine , Image Processing, Computer-Assisted , Reproducibility of ResultsABSTRACT
Oxidative stress caused by light and high temperature arises during in vitro maturation (IVM), resulting in low-quality embryos compared with those obtained in vivo. To overcome this problem, we investigated the influence of piperine (PIP) treatment during maturation of porcine oocytes on subsequent embryo development in vitro. Porcine oocytes were cultured in IVM medium supplemented with 0, 50, 100, 200, or 400 µM PIP. After parthenogenetic activation, the blastocyst (BL) formation was significantly higher and the apoptosis rate was significantly lower using 200 µM PIP-treated oocytes (200 PIP). In the 200 PIP group, the level of reactive oxygen species at the metaphase II stage was decreased, accompanied by an increased level of glutathione and increased expression of antioxidant processes (Nrf2, CAT, HO-1, SOD1, and SOD2). Consistently, chromosome misalignment and aberrant spindle organization were alleviated and phosphorylated p44/42 mitogen-activated protein kinase activity was increased in the 200 PIP group. Expression of development-related (CDX2, NANOG, POU5F1, and SOX2), anti-apoptotic (BCL2L1 and BIRC5), and pro-apoptotic (BAK, FAS, and CASP3) processes was altered in the 200 PIP group. Ultimately, embryo development was improved in the 200 PIP group following somatic cell nuclear transfer. These findings suggest that PIP improves the quality of porcine oocytes by reducing oxidative stress, which inevitably arises via IVM. In-depth mechanistic studies of porcine oocytes will improve the efficiencies of assisted reproductive technologies.
Subject(s)
Alkaloids , Benzodioxoles , Blastocyst , In Vitro Oocyte Maturation Techniques , Piperidines , Polyunsaturated Alkamides , Swine , Animals , In Vitro Oocyte Maturation Techniques/methods , Blastocyst/metabolism , Oocytes/metabolism , Oxidative Stress , Embryonic Development , Reactive Oxygen Species/metabolismABSTRACT
Objective: The inflammatory microenvironment has been implicated in differentiated thyroid cancer (DTC). Inflammatory stimuli induce the release of components of neutrophils into extracellular space, leading to formation of neutrophil extracellular trap (NET), which can stimulate growth and progression of cancer. Generation of activated factor XII and thrombin is also involved in cancer progression. This study attempted to determine whether the level of circulating markers of NET, activated factor XII, and endogenous thrombin potential may be useful for detecting the recurrence of DTC. Methods: A total of 122 patients with DTC were recruited during the postoperative follow-up period. Measurement of the levels of circulating markers of NET (neutrophil elastase, histone-DNA complex, cell-free dsDNA), activated factor XII, and endogenous thrombin potential was performed. Results: A significantly elevated level of neutrophil elastase was detected in patients with recurrence (n = 12) compared to those without recurrence (n = 110), while significant elevation of the levels of other markers was not observed. The value for area under the curve (0.717, P = 0.018) of neutrophil elastase for detecting recurrence of DTC was superior to that (0.661, P = 0.051) of serum thyroglobulin. An elevated level of neutrophil elastase was significantly associated with recurrence of DTC independent of serum thyroglobulin. Conclusions: Because an elevated level of neutrophil elastase was detected in patients with recurrence of DTC and showed a significant association with recurrence of DTC, it can be proposed as a novel biomarker for use in detecting recurrence of DTC along with other tests.
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PURPOSE: This study evaluated the feasibility and utility of longitudinal cough frequency monitoring with the Hyfe Cough Tracker, a mobile application equipped with cough-counting artificial intelligence algorithms, in real-world patients with chronic cough. METHODS: Patients with chronic cough (> 8-week duration) were monitored continuously for cough frequency with the Hyfe app for at least one week. Cough was also evaluated using the Leicester Cough Questionnaire (LCQ) and daily cough severity scoring (0-10). The study analyzed adherence rate, the correlation between objective cough frequency and subjective scores, day-to-day variability, and patient experience. RESULTS: Of 65 subjects consecutively recruited, 43 completed the study. The median cough monitoring duration was 13.9 days, with a median adherence of 91%. Study completion was associated with baseline cough severity, and the adherence rate was higher in younger subjects. Cross-sectional correlation analyses showed modest correlations between objective and subjective cough measures at the group level. However, in time series correlation analyses, correlations between objective and subjective measures widely varied across individuals. Cough frequency had greater day-to-day variability than daily cough severity scores in most subjects. A patient experience survey found that 70% of participants found the cough monitoring helpful, 86% considered it acceptable, and 84% felt it was easy to use. CONCLUSION: Monitoring cough frequency longitudinally for at least one week may be feasible. The substantial day-to-day variability in objective cough frequency highlights the need for continuous monitoring. Grasping the implications of daily cough variability is crucial in both clinical practice and clinical trials.
Subject(s)
Mobile Applications , Humans , Cough/diagnosis , Cough/drug therapy , Smartphone , Artificial Intelligence , Feasibility Studies , Cross-Sectional Studies , Chronic DiseaseABSTRACT
Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.
Subject(s)
Signal Transduction , Transcription Factors , Animals , Mice , Amphiregulin/genetics , Mice, Knockout , Social Dominance , Transcription Factors/metabolismABSTRACT
Background In patients with multiple myeloma (MM), the serum marker ß2-microglobulin does not always accurately reflect tumor load. In contrast, whole-body (WB) MRI has shown high sensitivity for detecting bone lesions. Purpose To develop and validate a semiquantitative WB MRI scoring system for newly diagnosed MM and to compare it with the International Staging System (ISS) and Revised ISS (R-ISS). Materials and Methods This study included two retrospective groups (group 1, July 2015 to September 2021; group 2, February 2020 to September 2021) and one prospective group (group 3, October 2021 to February 2022) of patients with newly diagnosed MM. A new scoring system for MM was developed using spine MRI scans in group 1 and WB MRI scans in group 2 that integrated three features: (a) background marrow pattern, (b) number of focal bone lesions, and (c) presence of extramedullary or paramedullary lesions. The summed total score ranged from zero to nine. The interobserver agreement for each feature was assessed using Fleiss or Cohen weighted κ. WB MRI total scores in group 3 were compared across ISS and R-ISS stages using two-way analysis of variance. Results Groups 1, 2, and 3 included 103 patients (mean age, 62.1 years ± 9.1 [SD]; 60 men), 36 patients (mean age 65.4 years ± 11.3 [SD]; 19 women), and 39 participants (mean age, 62.0 years ± 11.7 [SD]; 20 men), respectively. The interobserver agreements for the three features composing the scoring system were substantial (κ range, 0.69-0.80). WB MRI total score increased with increasing ISS stage (mean score for ISS 1, 2, and 3 was 2.2, 4.2, and 5.8, respectively; P = .009) and R-ISS stage (mean score for R-ISS 1, 2, and 3 was 2.1, 3.8, and 5.9, respectively; P = .005). Conclusion The developed WB MRI scoring system for MM demonstrated substantial observer agreement and corresponded well with ISS and R-ISS stages. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Dragan and Messiou in this issue.