Computed tomography radiomics models of tumor differentiation in canine small intestinal tumors.

Radiomics models have been widely exploited in oncology for the investigation of tumor classification, as well as for predicting tumor response to treatment and genomic sequence; however, their performance in veterinary gastrointestinal tumors remains unexplored. Here, we sought to investigate and compare the performance of radiomics models in various settings for differentiating among canine small intestinal adenocarcinoma, lymphoma, and spindle cell sarcoma. Forty-two small intestinal tumors were contoured using four different segmentation methods: pre- or post-contrast, each with or without the inclusion of intraluminal gas. The mesenteric lymph nodes of pre- and post-contrast images were also contoured. The bin settings included bin count and bin width of 16, 32, 64, 128, and 256. Multinomial logistic regression, random forest, and support vector machine models were used to construct radiomics models. Using features from both primary tumors and lymph nodes showed significantly better performance than modeling using only the radiomics features of primary tumors, which indicated that the inclusion of mesenteric lymph nodes aids model performance. The support vector machine model exhibited significantly superior performance compared with the multinomial logistic regression and random forest models. Combining radiologic findings with radiomics features improved performance compared to using only radiomics features, highlighting the importance of radiologic findings in model building. A support vector machine model consisting of radiologic findings, primary tumors, and lymph node radiomics features with bin count 16 in post-contrast images with the exclusion of intraluminal gas showed the best performance among the various models tested. In conclusion, this study suggests that mesenteric lymph node segmentation and radiological findings should be integrated to build a potent radiomics model capable of differentiating among small intestinal tumors.

Improvement in Image Quality of Low-Dose CT of Canines with Generative Adversarial Network of Anti-Aliasing Generator and Multi-Scale Discriminator.

Computed tomography (CT) imaging is vital for diagnosing and monitoring diseases in both humans and animals, yet radiation exposure remains a significant concern, especially in animal imaging. Low-dose CT (LDCT) minimizes radiation exposure but often compromises image quality due to a reduced signal-to-noise ratio (SNR). Recent advancements in deep learning, particularly with CycleGAN, offer promising solutions for denoising LDCT images, though challenges in preserving anatomical detail and image sharpness persist. This study introduces a novel framework tailored for animal LDCT imaging, integrating deep learning techniques within the CycleGAN architecture. Key components include BlurPool for mitigating high-resolution image distortion, PixelShuffle for enhancing expressiveness, hierarchical feature synthesis (HFS) networks for feature retention, and spatial channel squeeze excitation (scSE) blocks for contrast reproduction. Additionally, a multi-scale discriminator enhances detail assessment, supporting effective adversarial learning. Rigorous experimentation on veterinary CT images demonstrates our framework's superiority over traditional denoising methods, achieving significant improvements in noise reduction, contrast enhancement, and anatomical structure preservation. Extensive evaluations show that our method achieves a precision of 0.93 and a recall of 0.94. This validates our approach's efficacy, highlighting its potential to enhance diagnostic accuracy in veterinary imaging. We confirm the scSE method's critical role in optimizing performance, and robustness to input variations underscores its practical utility.

Trend of prevalence and characteristics of preserved ratio impaired spirometry (PRISm): Nationwide population-based survey between 2010 and 2019.

PURPOSE: This study aimed to evaluate the prevalence, trends, and factors of preserved ratio with impaired spirometry (PRISm) by using a nationally representative sample. PATIENTS AND METHODS: The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used: of total 32,949 participants aged ≥40 and no missing data on spirometry, 24,523 with normal, 4,623 with obstructive, and 3,803 with PRISm were identified. PRISm was defined as FEV1/FVC ≥70% and FEV1% of the predicted value (%pred) <80. PRISm-lower limit of normal (LLN) was defined when FEV1/FVC ≥LLN and FEV1

Role of SYT11 in human pan-cancer using comprehensive approaches.

BACKGROUND: Synaptotagmin 11 (SYT11) plays a pivotal role in neuronal vesicular trafficking and exocytosis. However, no independent prognostic studies have focused on various cancers. In this study, we aimed to summarize the clinical significance and molecular landscape of SYT11 in various tumor types. METHODS: Using several available public databases, we investigated abnormal SYT11 expression in different tumor types and its potential clinical association with prognosis, methylation profiling, immune infiltration, gene enrichment analysis, and protein-protein interaction analysis, and identified common pathways. RESULTS: TCGA and Genotype-Tissue Expression (GTEx) showed that SYT11 was widely expressed across tumor and corresponding normal tissues. Survival analysis showed that SYT11 expression correlated with the prognosis of seven cancer types. Additionally, SYT11 mRNA expression was not affected by promoter methylation, but regulated by certain miRNAs and associated with cancer patient prognosis. In vitro experiments further verified a negative correlation between the expression of SYT11 and miR-19a-3p in human colorectal, lung, and renal cancer cell lines. Moreover, aberrant SYT11 expression was significantly associated with immune infiltration. Pathway enrichment analysis revealed that the biological and molecular processes of SYT11 were related to clathrin-mediated endocytosis, Rho GTPase signaling, and cell motility-related functions. CONCLUSIONS: Our results provide a clear understanding of the role of SYT11 in various cancer types and suggest that SYT11 may be of prognostic and clinical significance.

Prevalence and confounders of chronic endometritis diagnosed using CD138 in patients with recurrent implantation failure.

OBJECTIVE: This retrospective study aimed to investigate the prevalence of chronic endometritis, diagnosed using CD138 immunohistochemistry, among infertile women and to assess the association between chronic endometritis and recurrent implantation failure (RIF). METHODS: In total, 266 patients who underwent hysteroscopy due to infertility between 2019 and 2020 were included in the analysis. Of these, 136 patients with RIF and 130 non-RIF patients were included in the study. CD138 immunohistochemistry test results, blood biomarkers (including natural killer cells, white blood cells, and the lymphocyte-to-neutrophil ratio), and data on pregnancy outcomes were obtained. If the CD138 test yielded a positive result, the patients received antibiotic treatment. RESULTS: The overall proportion of CD138-positive patients was 32.7% (87/266). The CD138 positivity rate was not related to the number of cycles with implantation failure. In the RIF patient group, no significant associations were found between CD138 positivity and peripheral blood markers. The clinical pregnancy rates were similar between infertile women treated with antibiotics for chronic endometritis and those without chronic endometritis. CONCLUSION: To improve the pregnancy rate in infertile patients, it may be helpful to combine CD138 testing with other laboratory tests and administer antibiotic treatment if the result is positive.

Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells.

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells. [BMB Reports 2023; 56(11): 612-617].

Weakly coordinated Li ion in single-ion-conductor-based composite enabling low electrolyte content Li-metal batteries.

The pulverization of lithium metal electrodes during cycling recently has been suppressed through various techniques, but the issue of irreversible consumption of the electrolyte remains a critical challenge, hindering the progress of energy-dense lithium metal batteries. Here, we design a single-ion-conductor-based composite layer on the lithium metal electrode, which significantly reduces the liquid electrolyte loss via adjusting the solvation environment of moving Li+ in the layer. A Li||Ni0.5Mn0.3Co0.2O2 pouch cell with a thin lithium metal (N/P of 2.15), high loading cathode (21.5 mg cm-2), and carbonate electrolyte achieves 400 cycles at the electrolyte to capacity ratio of 2.15 g Ah-1 (2.44 g Ah-1 including mass of composite layer) or 100 cycles at 1.28 g Ah-1 (1.57 g Ah-1 including mass of composite layer) under a stack pressure of 280 kPa (0.2 C charge with a constant voltage charge at 4.3 V to 0.05 C and 1.0 C discharge within a voltage window of 4.3 V to 3.0 V). The rational design of the single-ion-conductor-based composite layer demonstrated in this work provides a way forward for constructing energy-dense rechargeable lithium metal batteries with minimal electrolyte content.

Prevalence, Trend, and Risk Factors for Early Chronic Obstructive Pulmonary Disease: An Analysis of the Nationwide Population-Based Survey from 2010 to 2019 in South Korea.

This study aimed to evaluate the prevalence, trends, and risk factors of early chronic obstructive pulmonary disease (COPD) by using a nationally representative sample. The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used, where 80,860 individuals were identified; of these, 9,045 participants aged 40-49 years who underwent spirometry with no missing data were analyzed. Early COPD was defined as forced expiratory volume in 1 s /forced vital capacity ratio < the lower limit of normal (2.5th percentile) in individuals aged <50 years without a history of asthma, inhaler therapy, or persistent respiratory symptoms. The prevalence and trend of early COPD were estimated according to features such as smoking status and pack-years. Joinpoint regression analysis was used to analyze the significant annual change in the trend according to sex, smoking status, and pack-years. A complex sample multivariable-adjusted regression model was used to identify factors affecting early COPD. The estimated population size during 2010-2019 was 82,326,178. Early COPD was present in 4.5% of patients (6.5% of men and 2.3% of women). It was present in 7.7% of current smokers, followed by former and never smokers. Among smokers with ≥ 10 pack-years, early COPD was present in 8.2%, whereas it was present in 2.6% of smokers with < 10 pack-years. Joinpoint regression analyses found a recent decrease in the trend of prevalence in males who were former and current smokers. The multivariable-adjusted logistic regression model showed that being male, lower educational level, smoking status, and pack-years were factors that affected the presence of early COPD. Continued surveillance of this pre-disease condition is required, and further research are warrant.

Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from eczema, itching, disrupted barrier function and aberrant cutaneous immune responses. The aim of the present study was to assess the efficacy of kushenol F as an effective treatment for AD via the suppression of thymic stromal lymphopoietin (TSLP) production. The results of the present study demonstrated that the clinical symptoms of AD were less severe and there was reduced ear thickening and scratching behavior in kushenol F-treated Dermatophagoides farinae extract (DFE)/1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Histopathological analysis demonstrated that kushenol F decreased the DFE/DNCB-induced infiltration of eosinophil and mast cells and TSLP protein expression levels. Furthermore, kushenol F-treated mice exhibited significantly lower concentrations of serum histamine, IgE and IgG2a compared with the DFE/DNCB-induced control mice. Kushenol F also significantly decreased phosphorylated NF-κB and IKK levels and the mRNA expression levels of IL-1ß and IL-6 in cytokine combination-induced human keratinocytes. The results of the present study suggested that kushenol F may be a potential therapeutic candidate for the treatment of AD via reducing TSLP levels.

Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1ß and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA.

Parametric and non-parametric estimation of reference intervals for routine laboratory tests: an analysis of health check-up data for 260 889 young men in the South Korean military.

OBJECTIVES: Determination of reference intervals (RIs) using big data faces several obstacles due to heterogeneity in analysers, period and ethnicity. The present study aimed to establish the RIs for routine common blood count (CBC) and biochemistry laboratory tests in homogeneous, healthy, male Korean soldiers in their 20s using a large health check-up data set, comparing parametric and non-parametric estimation. DESIGN: A multicentre, cross-sectional study. SETTING: Seven armed forces hospitals in South Korea. PARTICIPANTS: A total of 609 649 men underwent health examination when promoted to corporal between January 2015 and September 2021. 260 889 eligible individuals aged 20-25 were included in the analysis. MAIN OUTCOMES AND MEASURES: The RIs were established by parametric and non-parametric methods. In the parametric approach, maximum likelihood estimation was applied to measure the Box-Cox transformation parameter and the values at the 2.5th and 97.5th percentiles were recalculated. The non-parametric approach adopted the Tukey's exclusion test and the values at the 2.5th and 97.5th percentiles were obtained. Classification by body mass index was also performed. RESULTS: The obtained RIs for haematology parameters were comparable between devices. If the values followed a Gaussian distribution, parametric and non-parametric methods were well matched for haematology and biochemical markers. When the values were right-skewed, the upper limits were higher with parametric than with non-parametric methods. Participants with obesity showed higher RIs for CBC, some liver function tests and some lipid profiles than participants without obesity. CONCLUSIONS: Using data from healthy, male Korean soldiers in their 20s, we proposed the RIs for CBC and biochemical parameters, comparing parametric and non-parametric estimation. As such approaches based on large data sets become more prevalent, further studies are needed to discriminate eligible individuals and determine RIs in an extrapolated sample.

Obstructive Sleep Apnea and Nonalcoholic Fatty Liver Disease in the General Population: A Cross-Sectional Study Using Nationally Representative Data.

(1) Background: To evaluate the association between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) in the general population using a nationally representative sample from South Korea; (2) Methods: This study included 4275 adults aged ≥40 years who completed the snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, and gender (STOP-Bang) questionnaire. The risk of OSA was stratified into low, intermediate, and high grades according to the STOP-Bang score. The prevalence of NAFLD according to the STOP-Bang score was calculated, and the increasing trend was measured. A complex sample multivariable regression analysis with adjustments for possible confounding variables was used to calculate the odds ratio of NAFLD and advanced fibrosis. Subgroup analysis was conducted with stratification based on sex and obesity status; (3) Results: We identified 1021 adults with NAFLD and 3254 adults without NAFLD. The prevalence of NAFLD increased significantly with higher STOP-Bang scores in both men and women. Participants of both sexes with high STOP-Bang scores were more likely to have NAFLD. Compared to non-obese individuals, the risk of NAFLD according to the STOP-Bang score was more intense in obese individuals. With respect to hepatic steatosis, there was no significant association between advanced fibrosis and STOP-Bang score; (4) Conclusions: OSA, the risk of which was measured using the STOP-Bang model, was closely associated with NAFLD in both Korean men and women. Clinicians should consider screening for NAFLD in individuals with a high STOP-Bang score.

TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis.

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-α (TNF-α) using Western blotting and immunofluorescence. Arthritis was induced in PINK1-/- mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-α treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1-/- mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA.

Effects of Different Centrifugation Protocols on the Detection of EGFR Mutations in Plasma Cell-Free DNA.

OBJECTIVES: Various preanalytical factors, including the collection tube, storage conditions, and centrifugation, affect the detection results of plasma cell-free DNA (cfDNA). We compared the effect of different centrifugation protocols on the detection of EGFR mutations in cfDNA. METHODS: We analyzed 117 plasma specimens from 110 patients with non-small cell lung cancer using the cobas EGFR Mutation Test v2 (Roche Diagnostics). We compared the identified EGFR mutations and semiquantitative index values from the 1- and 2-step centrifugation groups and confirmed the clinical impact of differences in the results after further high-speed centrifugation. RESULTS: We detected EGFR mutations in 44 (37.6%) and 47 (40.2%) samples that were centrifuged once and twice, respectively; the 2 groups showed an 89.7% (105/117) concordance and a strong correlation in their semiquantitative index values (r = 0.929). Among the 12 inconsistent result pairs, 9 samples of 2-step centrifugation (75%) were consistent with the results of a recent tissue biopsy. CONCLUSIONS: Additional high-speed centrifugation has been shown to increase the sensitivity of EGFR mutation detection in a commercial in vitro diagnostic real-time polymerase chain reaction device and is an optimal preanalytical factor for detecting low-allele frequency gene mutations using low concentrations of cfDNA.

Immunogenicity after Second ChAdOx1 nCoV-19 (AZD1222) Vaccination According to the Individual Reactogenicity, Health Status and Lifestyle.

The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals' sex, age, and BMI were found to be associated with immunogenicity after vaccination.

Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration.

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

RNA demethylation by FTO stabilizes the FOXJ1 mRNA for proper motile ciliogenesis.

Adenosine N6-methylation (m6A) is one of the most pervasive mRNA modifications, and yet the physiological significance of m6A removal (demethylation) remains elusive. Here, we report that the m6A demethylase FTO functions as a conserved regulator of motile ciliogenesis. Mechanistically, FTO demethylates and thereby stabilizes the mRNA that encodes the master ciliary transcription factor FOXJ1. Depletion of Fto in Xenopus laevis embryos caused widespread motile cilia defects, and Foxj1 was identified as one of the major phenocritical targets. In primary human airway epithelium, FTO depletion also led to FOXJ1 mRNA destabilization and a severe loss of ciliated cells with an increase of neighboring goblet cells. Consistently, Fto knockout mice showed strong asthma-like phenotypes upon allergen challenge, a result owing to defective ciliated cells in the airway epithelium. Altogether, our study reveals a conserved role of the FTO-FOXJ1 axis in embryonic and homeostatic motile ciliogenesis.

Pancreatic cancer induces muscle wasting by promoting the release of pancreatic adenocarcinoma upregulated factor.

Cancer cachexia is a highly debilitating condition characterized by weight loss and muscle wasting that contributes significantly to the morbidity and mortality of pancreatic cancer. The factors that induce cachexia in pancreatic cancer are largely unknown. We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis. Here, we analyzed the relation between pancreatic cancer-derived PAUF and cancer cachexia in mice and its clinical significance. Body weight loss and muscle weight loss were significantly higher in mice with Panc-1/PAUF tumors than in those with Panc-1/Mock tumors. Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice. C2C12 myotubes treated with rPAUF exhibited rapid inactivation of Akt-Foxo3a signaling, resulting in Atrogin1/MAFbx upregulation, myosin heavy chain loss, and muscle atrophy. The neutrophil-to-lymphocyte ratio and body weight loss were significantly higher in pancreatic cancer patients with high PAUF expression than in those with low PAUF expression. Analysis of different pancreatic cancer datasets showed that PAUF expression was significantly higher in the pancreatic cancer group than in the nontumor group. Analysis of The Cancer Genome Atlas data found associations between high PAUF expression or a high DNA copy number and poor overall survival. Our data identified tumor-secreted circulating PAUF as a key factor of cachexia, causing muscle wasting in mice. Neutralizing PAUF may be a useful therapeutic strategy for the treatment of pancreatic cancer-induced cachexia.