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In vitro organoids that mimic the physiological properties of in vivo organs based on threedimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.
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Background/Objectives: Pancreatic stone protein (PSP) is an emerging biomarker of sepsis that is secreted from pancreas sensing remote organ damages. We explored the diagnostic and prognostic utilities of PSP in patients with suspected sepsis. Methods: In a total of 285 patients (suspected sepsis, n = 148; sepsis, n = 137), we compared PSP with procalcitonin (PCT) and sequential organ failure assessment (SOFA) score. Sepsis diagnoses were explored using receiver operating characteristic curve analyses with area under the curves (AUCs). Clinical outcomes (in-hospital mortality, 30-day mortality, and kidney replacement therapy [KRT]) were explored using the Kaplan-Meier method and a multivariate analysis with hazard ratio (HR). Results: PCT and PSP were comparable for sepsis diagnosis (AUC = 0.71-0.72, p < 0.001). The sepsis proportion was significantly higher when both biomarkers increased than when either one or both biomarkers did not increase (89.0% vs. 21.3-47.7%, p < 0.001). Each biomarker quartile (Q1-Q4) differed significantly according to their SOFA score (all p < 0.001). Compared with Q1, the Q2-Q4 groups showed worse clinical outcomes (p = 0.002-0.041). Both biomarkers added to the SOFA score showed higher HRs than the SOFA score alone (3.3-9.6 vs. 2.8-4.2, p < 0.001-0.011), with nearly 2.5-fold higher HR (9.6 vs. 4.2) for predicting KRT. Conclusions: Although PCT and PSP did not independently predict clinical outcomes in the multivariate analysis, PSP demonstrated diagnostic and prognostic utilities in patients with suspected sepsis, especially for predicting kidney dysfunction. PSP, alone or in combination with PCT, would be a valuable tool that can be added to clinical assessments.
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This study aimed to analyze bacterial communities in breast milk obtained from five breastfeeding women. Culture-dependent and culture-independent methods were used to analyze microbial communities. Total bacterial count of breast milk determined using plate count agar ranged from 3.3 × 104 ± 3.5 × 102 colony forming unit (CFU)/g to 1.7 × 105 ± 3.5 × 103 CFU/g, with a pH between 6.4 and 6.8. Only three species, Leuconostoc citreum (17 out of 160 strains; 10.63%), Staphylococcus epidermidis (118 strains; 73.75%), and Staphylococcus lugdunensis (25 strains; 15.63%), belong to the phylum Bacillota were detected by culture-dependent analysis. Microbial communities analyzed via pyrosequencing revealed greater diversity compared to the culture-dependent analysis. At the phylum level, Bacillota accounted for 60.9% of the microbial community. At the genus level, Staphylococcus (24.57%), Streptococcus (22.93%), and Methylobacterium (8.76%) were dominant genera. While pyrosequencing demonstrated greater microbial diversity than the agar plate culture method, identified microbes might lack information or include many unculturable microbes. Most of all, considering the low total bacterial count averaging 7.2 × 104 CFU/g, further research is needed to determine the significance of microbial presence in breast milk.
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Bacterias , Lactancia Materna , Leche Humana , Leche Humana/microbiología , Humanos , Femenino , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Microbiota , ARN Ribosómico 16S/genética , Biodiversidad , Adulto , Carga Bacteriana , ADN Bacteriano/genética , Análisis de Secuencia de ADN , FilogeniaRESUMEN
Lactiplantibacillus (Lb.) plantarum is known as a benign bacterium found in various habitats, including the intestines of animals and fermented foods. Since animal intestines lack oxygen, while fermented foods provide a limited or more oxygen environment, this study aimed to investigate whether there were genetic differences in the growth of Lb. plantarum under aerobic vs. anaerobic conditions. Genomic analysis of Lb. plantarum obtained from five sources-animals, dairy products, fermented meat, fermented vegetables, and humans-was conducted. The analysis included not only an examination of oxygen-utilizing genes but also a comparative pan-genomic analysis to investigate evolutionary relationships between genomes. The ancestral gene analysis of the evolutionary pathway classified Lb. plantarum into groups A and B, with group A further subdivided into A1 and A2. It was confirmed that group A1 does not possess the narGHIJ operon, which is necessary for energy production under limited oxygen conditions. Additionally, it was found that group A1 has experienced more gene acquisition and loss compared to groups A2 and B. Despite an initial assumption that there would be genetic distinctions based on the origin (aerobic or anaerobic conditions), it was observed that such differentiation could not be attributed to the origin. However, the evolutionary process indicated that the loss of genes related to nitrate metabolism was essential in anaerobic or limited oxygen conditions, contrary to the initial hypothesis.
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Evolución Molecular , Oxígeno , Oxígeno/metabolismo , Filogenia , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Genoma Bacteriano , Anaerobiosis , Animales , HumanosRESUMEN
Human apolipoprotein E (ApoE) was first identified as a polymorphic gene in the 1970s; however, the genetic association of ApoE genotypes with late-onset sporadic Alzheimer's disease (sAD) was only discovered 20 years later. Since then, intensive research has been undertaken to understand the molecular effects of ApoE in the development of sAD. Despite three decades' worth of effort and over 10,000 papers published, the greatest mystery in the ApoE field remains: human ApoE isoforms differ by only one or two amino acid residues; what is responsible for their significantly distinct roles in the etiology of sAD, with ApoE4 conferring the greatest genetic risk for sAD whereas ApoE2 providing exceptional neuroprotection against sAD. Emerging research starts to point to a novel and compelling hypothesis that the sialoglycans posttranslationally appended to human ApoE may serve as a critical structural modifier that alters the biology of ApoE, leading to the opposing impacts of ApoE isoforms on sAD and likely in the peripheral systems as well. ApoE has been shown to be posttranslationally glycosylated in a species-, tissue-, and cell-specific manner. Human ApoE, particularly in brain tissue and cerebrospinal fluid (CSF), is highly glycosylated, and the glycan chains are exclusively attached via an O-linkage to serine or threonine residues. Moreover, studies have indicated that human ApoE glycans undergo sialic acid modification or sialylation, a structural alteration found to be more prominent in ApoE derived from the brain and CSF than plasma. However, whether the sialylation modification of human ApoE has a biological role is largely unexplored. Our group recently first reported that the three major isoforms of human ApoE in the brain undergo varying degrees of sialylation, with ApoE2 exhibiting the most abundant sialic acid modification, whereas ApoE4 is the least sialylated. Our findings further indicate that the sialic acid moiety on human ApoE glycans may serve as a critical modulator of the interaction of ApoE with amyloid ß (Aß) and downstream Aß pathogenesis, a prominent pathologic feature in AD. In this review, we seek to provide a comprehensive summary of this exciting and rapidly evolving area of ApoE research, including the current state of knowledge and opportunities for future exploration.
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This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of -9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties.
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Antioxidantes , Metabolómica , Simulación del Acoplamiento Molecular , Oryza , Oryza/química , Oryza/metabolismo , Antioxidantes/química , Antioxidantes/metabolismoRESUMEN
Sarcopenia refers to an age-related decrease in muscle mass and strength. The gut-muscle axis has been proposed as a promising target to alleviate muscle atrophy. The effect of KL-Biome-a postbiotic preparation comprising heat-killed Lactiplantibacillus plantarum KM-2, its metabolites, and an excipient (soybean powder)-on muscle atrophy was evaluated using dexamethasone (DEX)-induced atrophic C2C12 myoblasts and C57BL/6J mice. KL-Biome significantly downregulated the expression of genes (Atrogin-1 and MuRF1) associated with skeletal muscle degradation but increased the anabolic phosphorylation of FoxO3a, Akt, and mTOR in C2C12 cells. Oral administration of KL-Biome (900 mg/kg) for 8 weeks significantly improved muscle mass, muscle function, and serum lactate dehydrogenase levels in DEX-treated mice. KL-Biome administration increased gut microbiome diversity and reversed DEX-mediated gut microbiota alterations. Furthermore, it significantly increased the relative abundances of the genera Subdologranulum, Alistipes, and Faecalibacterium prausnitzii, which are substantially involved in short-chain fatty acid production. These findings suggest that KL-Biome exerts beneficial effects on muscle atrophy by regulating gut microbiota.
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Dexametasona , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Músculo Esquelético , Atrofia Muscular , Animales , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/inducido químicamente , Ratones , Dexametasona/farmacología , Dexametasona/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Masculino , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas Ligasas SKP Cullina F-box/metabolismo , Proteínas Ligasas SKP Cullina F-box/genética , Probióticos/administración & dosificación , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Sarcopenia/tratamiento farmacológico , Sarcopenia/metabolismo , Sarcopenia/patología , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular , Lactobacillus plantarumRESUMEN
The gold standard test for diagnosing dysphagia is the videofluoroscopic swallowing study (VFSS). However, the accuracy of this test varies depending on the specialist's skill level. We proposed a VFSS-based artificial intelligence (AI) web application to diagnose dysphagia. Video from the VFSS consists of multiframe data that contain approximately 300 images. To label the data, the server separated them into frames during the upload and stored them as a video for analysis. Then, the separated data were loaded into a labeling tool to perform the labeling. The labeled file was downloaded, and an AI model was developed by training with You Only Look Once (YOLOv7). Using a utility called SplitFolders, the entire dataset was divided according to a ratio of training (70%), test (10%), and validation (20%). When a VFSS video file was uploaded to an application equipped with the developed AI model, it was automatically classified and labeled as oral, pharyngeal, or esophageal. The dysphagia of a person was categorized as either penetration or aspiration, and the final analyzed result was displayed to the viewer. The following labeling datasets were created for the AI learning: oral (n = 2355), pharyngeal (n = 2338), esophageal (n = 1480), penetration (n = 1856), and aspiration (n = 1320); the learning results of the YOLO model, which analyzed dysphagia using the dataset, were predicted with accuracies of 0.90, 0.82, 0.79, 0.92, and 0.96, respectively. This is expected to help clinicians more efficiently suggest the proper dietary options for patients with oropharyngeal dysphagia.
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Microplastic (MP) pollution in urban environments is a pervasive and complex problem with significant environmental and human health implications. Although studies have been conducted on MP pollution in urban environments, there are still research gaps in understanding the exact sources, regulation, and impact of urban MP on the environment and public health. Therefore, the goal of this study is to provide a comprehensive overview of the complex pathways, harmful effects, and regulatory efforts of urban MP pollution. It discusses the research challenges and suggests future directions for addressing MPs related to environmental issues in urban settings. In this study, original research papers published from 2010 to 2024 across ten database categories, including PubMed, Google Scholar, Scopus, and Web of Science, were selected and reviewed to improve our understanding of urban MP pollution. The analysis revealed multifaceted sources of MPs, including surface runoff, wastewater discharge, atmospheric deposition, and biological interactions, which contribute to the contamination of aquatic and terrestrial ecosystems. MPs pose a threat to marine and terrestrial life, freshwater organisms, soil health, plant communities, and human health through ingestion, inhalation, and dermal exposure. Current regulatory measures for MP pollution include improved waste management, upgraded wastewater treatment, stormwater management, product innovation, public awareness campaigns, and community engagement. Despite these regulatory measures, several challenges such as; the absence of standardized MPs testing methods, MPs enter into the environment through a multitude of sources and pathways, countries struggle in balancing trade interests with environmental concerns have hindered effective policy implementation and enforcement. Addressing MP pollution in urban environments is essential for preserving ecosystems, safeguarding public health, and advancing sustainable development. Interdisciplinary collaboration, innovative research, stringent regulations, and public participation are vital for mitigating this critical issue and ensuring a cleaner and healthier future for urban environments and the planet.
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Monitoreo del Ambiente , Microplásticos , Microplásticos/análisis , Humanos , Monitoreo del Ambiente/métodos , Contaminación Ambiental , Ciudades , Salud Pública , Contaminantes Químicos del Agua/análisisRESUMEN
Although endoscopic forceps biopsy is the gold standard for early gastric cancer (EGC) diagnosis, the method can cause endoscopic resection of specimens and histological discrepancies. This study aims to examine the risk factors for histological discrepancies in EGC and long-term clinical outcomes. This retrospective study included patients diagnosed with differentiated-type EGC using forceps biopsy. Patients without histological discrepancies and with undifferentiated types in endoscopic resection histology were categorized into the concordant and discordant groups, respectively. Clinical characteristics and long-term outcomes related to histological discrepancies were analyzed. A total of 957 lesions from 936 patients were enrolled. An overall discrepancy rate of 8.7% was confirmed, with an undifferentiated-type discrepancy of 5.5%. The discordant group showed a higher tendency for lesions to be located in the upper third region, to have whitish discoloration, and to undergo a greater number of biopsies compared with the concordant group. Multivariate analysis confirmed that lesion location in the upper third region (odds ratio [OR]: 2.125; 95% confidence interval [CI]: 1.032-5.277; Pâ =â .041) and whitish surface discoloration (OR: 13.615; 95% CI: 6.028-28.728; Pâ =â .001) were significantly correlated with histologic discrepancy. Compared with the concordant group, the discordant group had a lower curative resection rate, but no differences were observed in complications, local recurrence, or survival rates. Upper third location and whitish discoloration were risk factors for the histologic discrepancy between differentiated and undifferentiated types in patients with EGC. For curative resections performed in patients with EGC and histologic discrepancies and without additional treatment, careful follow-up is possible.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Riesgo , Anciano , Biopsia/métodos , Instrumentos Quirúrgicos , Gastroscopía/métodos , Detección Precoz del Cáncer/métodos , Resección Endoscópica de la Mucosa/métodosRESUMEN
ABSTRACT: This meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20×CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models estimated the complete response (CR) rate and secondary outcomes, with meta-regressions adjusting for relevant covariates. Sixteen studies comprising 1347 patients were included in the pooled analysis. The pooled CR rate for bispecific antibodies was 0.36 (95% confidence interval [CI], 0.29-0.43), compared with 0.51 (95% CI, 0.46-0.56) for CAR T-cell therapy (P < .01). This superiority persisted when comparing the CAR T-cell-naive patients within the bispecific antibody group, with a CR rate of 0.37 (95% CI, 0.32-0.43). Multivariable meta-regression also revealed better efficacy of CAR T cells with adjustment for the proportion of double-hit lymphoma. The pooled 1-year progression-free survival rate mirrored these findings (0.32 [95% CI, 0.26-0.38] vs 0.44 [95% CI, 0.41-0.48]; P < .01). For adverse events of grade ≥3, the bispecific antibody had incidences of 0.02 (95% CI, 0.01-0.04) for cytokine release syndrome, 0.01 (95% CI, 0.00-0.01) for neurotoxicity, and 0.10 (95% CI, 0.03-0.16) for infections. The CAR T cell had rates of 0.08 (95% CI, 0.03-0.12), 0.11 (95% CI, 0.06-0.17), and 0.17 (95% CI, 0.11-0.22), respectively, with significant differences observed in the first 2 categories. In summary, CAR T-cell therapy outperformed bispecific antibody in achieving higher CR rates, although with an increase in severe adverse events.
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Anticuerpos Biespecíficos , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/inmunología , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.
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Antineoplásicos Inmunológicos , Biosimilares Farmacéuticos , Neoplasias de la Mama , Vigilancia de Productos Comercializados , Neoplasias Gástricas , Trastuzumab , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Estudios Prospectivos , Receptor ErbB-2/genética , República de Corea , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Resultado del TratamientoRESUMEN
Attention toward the preventive effects of postbiotics on metabolic diseases has increased because of greater stability and safety over probiotics. However, studies regarding the bioactive effects of postbiotics, especially from probiotic Bacillus strains, are relatively limited. The anti-obesity effects of the cell-free culture supernatant of Bacillus velezensis KMU01 (CFS-B.vele) were evaluated using high-fat-diet (HFD)-induced mice. HFD-induced mice (n = 8 per group) received equal volumes of (1) CFS-B.vele (114 mg/kg) in PBS, (2) Xenical in PBS, or (3) PBS alone by oral gavage daily for 13 weeks. The results demonstrated that CFS-B.vele changed the gut microbiota and showed anti-obesity effects in HFD-induced obese mice. The elevated Firmicutes/Bacteroidota ratio induced by HFD was decreased in the CFS-B.vele group compared to the other groups (p < 0.05). The CFS-B.vele intervention led to the enrichment of SCFA-producers, such as Roseburia and Eubacterium, in the cecum, suggesting their potential involvement in the amelioration of obesity. Due to these changes, the various obesity-related biomarkers (body weight, fat in tissue, white adipose tissue weight and size, serum LDL-cholesterol level, hepatic lipid accumulation, and adipogenesis/lipogenesis-related gene/protein expression) were improved. Our findings suggest that CFS-B.vele has potential as a novel anti-obesity agent through modulation of the gut microbiota.
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Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.
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Derivados del Benceno , Resección Endoscópica de la Mucosa , Imidazoles , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Esomeprazol/uso terapéutico , Úlcera/tratamiento farmacológico , Úlcera/etiología , Inhibidores de la Bomba de Protones/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/cirugía , Úlcera Gástrica/etiología , Neoplasias Gástricas/etiología , Resección Endoscópica de la Mucosa/efectos adversosRESUMEN
Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy. For non-metastatic ccRCC, increased CD8+ T cell infiltration was associated with a reduced likelihood of progression to metastatic disease. Interestingly, patients who progressed to metastatic disease also had increased percentages of exhausted CD8+ T cells. Finally, we evaluated the spatial heterogeneity of the immune infiltration and demonstrated that patients without metastatic progression had CD8+ T cells in closer proximity to ccRCC cells. These data strengthen the evidence for CD8+ T cell infiltration as a prognostic biomarker in non-metastatic ccRCC and demonstrate that multi-region sampling may be necessary to fully characterize immune infiltration within heterogeneous tumors. Tumor CD8+ T cell infiltration should be investigated as a biomarker in adjuvant systemic therapy clinical trials for high-risk non-metastatic RCC.
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BACKGROUND AND AIMS: This study aimed to validate Helicobacter pylori serological and pepsinogen (PG) assays for detecting infection and gastric neoplasm. METHODS: Individuals who underwent serum Chorus H. pylori and HBI PG assays were included from May to September 2023. The GastroPanel test was performed using the same blood sample. HBI assay findings were interpreted with the ABC method using the criteria of corpus atrophy (PG I ≤ 70 ng/mL & I/II ≤3) and advanced corpus atrophy (PG I ≤ 30 ng/mL & I/II ≤2). RESULTS: A total of 144 H. pylori-infected and 184 non-infected Koreans were analyzed. The Chorus test (sensitivity 97.2%, specificity 89.1%) showed higher area under the curve (0.993 vs. 0.972, p = 0.003) than the GastroPanel test (sensitivity 95.8%, specificity 86.4%). Using the GastroSoft application, the incidence of gastric neoplasms was highest in the corpus atrophy group (50%), followed by the low acid-output (25.8%), H. pylori infection (11.6%), and antral atrophy (9.1%) groups. There were no gastric neoplasms in the normal and high acid output groups. Using the ABC method, the incidence of gastric neoplasms was highest in the corpus atrophy groups (23.8% in Groups C and D), followed by Group B (12.3%) and Group A (2.4%). Corpus atrophy interpreted with the GastroSoft showed poor agreement (k = 0.225) with corpus atrophy interpreted with the ABC method, whereas it showed excellent agreement (k = 0.854) with advanced corpus atrophy. CONCLUSIONS: Although the Chorus test was more accurate than the GastroPanel test, both assays discriminated high-risk individuals by detecting atrophy or infection. There were no gastric neoplasms in the normal or high acid-output groups (GastroSoft application), and gastric neoplasm incidence was lowest in Group A (ABC method). Corpus atrophy determined by GastroSoft application is more consistent with advanced corpus atrophy determined by the ABC method than is corpus atrophy.
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Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Pepsinógeno A , Estudios Prospectivos , Infecciones por Helicobacter/diagnóstico , AtrofiaRESUMEN
INTRODUCTION: A narrow safety margin (NSM) after endoscopic submucosal dissection (ESD) is a well-recognized risk factor for local recurrence in early gastric cancer (EGC). However, only a few studies have investigated the risk factors for the development of NSM. METHODS: The medical records and pathologic specimens of patients with EGC who underwent ESD from January 2020 to December 2020 at a single tertiary hospital (Daejeon, South Korea) were reviewed. RESULTS: A total of 218 patients were enrolled and 29 had NSM (<3 mm). When comparing the NSM and the control groups, the size of the lesion, the depth of invasion, and the operating endoscopist were found to be risk factors for the development of NSM. The increased length of the subepithelial spread of the lesion was associated with a narrower safety margin. Logistic regression analysis revealed that lesion size was a risk factor for NSM, and a marginally significant difference between endoscopists was found. CONCLUSIONS: Multiple factors may need to be considered during ESD, including lesion size, invasion depth, operating endoscopist, and subepithelial spread.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Factores de Riesgo , Resultado del TratamientoRESUMEN
We evaluated the diagnostic performance of the STANDARD i-Q COVID-19 Ag Test, which was developed to detect viral antigens, using nasal and oral swabs. Sixty positive and 100 negative samples were analyzed. We determined the distribution of the Ct values according to the day of sample collection after symptom onset, the diagnostic performance of the total samples and subgroups separated by Ct value or time of sample collection, and the Ct value at which maximal accuracy was expected. No differences were observed in Ct values, except for the samples obtained on the day of symptom onset. The diagnostic sensitivity and specificity of the oral swabs were 75.0 and 100.0%, respectively, whereas those of the nasal swabs were 85.0 and 98.0%, respectively. The sensitivity was higher in samples with a high viral load collected earlier than those collected later, although the difference was not significant. False-negative results were confirmed in all samples with a Ct value ≥ 30.0. These results indicate that tests using oral and nasal swabs are helpful for diagnosing acute symptomatic cases with suspected high viral loads. Our tests exhibited relatively low sensitivity but high specificity rates, indicating the need to assess negative antigen test results.
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Youth exposed to chronic stress exhibit increased cardiometabolic risk which parental social support may attenuate. Notably, theories emphasize that support should be delivered responsively for it to exert buffering effects, but this has not been thoroughly tested empirically. This study examined whether timing of support is an important but unrecognized element of responsiveness during adolescence in buffering the link between chronic stress and cardiometabolic risk. Participants were 242 adolescents aged 15 years (63 % female, 38 % Black). Adolescents completed assessments of chronic stress (Life Stress Interview), and trained personnel collected anthropometric measures and blood samples to assess cardiometabolic risk (reflected in low-grade inflammation and metabolic syndrome). Adolescents also completed an eight-day diary assessment to report daily stressor exposure and parental support. Using the diary data, responsiveness of parental support was operationalized as the within-individual difference in parental support received on stressor (vs. non-stressor) days, such that increased parental support on stressor days reflected more timely support. Results suggest that responsive parental support buffered the link between chronic stress and cardiovascular risk. Specifically, chronic stress was associated with greater risk only when parental support was not temporally aligned with stress exposure, but this association was not observed among adolescents who received timely parental support. These findings shed light on why parental support may not always exert buffering effects during adolescence, highlighting the importance of taking a developmental approach to understanding protective effects.
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Enfermedades Cardiovasculares , Síndrome Metabólico , Humanos , Adolescente , Femenino , Masculino , Apoyo Social , Padres , InflamaciónRESUMEN
BACKGROUND. Screening mammography has decreased performance in patients with dense breasts. Supplementary screening ultrasound is a recommended option in such patients, although it has yielded mixed results in prior investigations. OBJECTIVE. The purpose of this article is to compare the performance characteristics of screening mammography alone, standalone artificial intelligence (AI), ultrasound alone, and mammography in combination with AI and/or ultrasound in patients with dense breasts. METHODS. This retrospective study included 1325 women (mean age, 53 years) with dense breasts who underwent both screening mammography and supplementary breast ultrasound within a 1-month interval from January 2017 to December 2017; prior mammography and prior ultrasound examinations were available for comparison in 91.2% and 91.8%, respectively. Mammography and ultrasound examinations were interpreted by one of 15 radiologists (five staff; 10 fellows); clinical reports were used for the present analysis. A commercial AI tool was used to retrospectively evaluate mammographic examinations for presence of cancer. Screening performances were compared among mammography, AI, ultrasound, and test combinations, using generalized estimating equations. Benign diagnoses required 24 months or longer of imaging stability. RESULTS. Twelve cancers (six invasive ductal carcinoma; six ductal carcinoma in situ) were diagnosed. Mammography, standalone AI, and ultrasound showed cancer detection rates (per 1000 patients) of 6.0, 6.8, and 6.0 (all p > .05); recall rates of 4.4%, 11.9%, and 9.2% (all p < .05); sensitivity of 66.7%, 75.0%, and 66.7% (all p > .05); specificity of 96.2%, 88.7%, and 91.3% (all p < .05); and accuracy of 95.9%, 88.5%, and 91.1% (all p < .05). Mammography with AI, mammography with ultrasound, and mammography with both ultrasound and AI showed cancer detection rates of 7.5, 9.1, and 9.1 (all p > .05); recall rates of 14.9, 11.7, and 21.4 (all p < .05); sensitivity of 83.3%, 100.0%, and 100.0% (all p > .05); specificity of 85.8%, 89.1%, and 79.4% (all p < .05); and accuracy of 85.7%, 89.2%, and 79.5% (all p < .05). CONCLUSION. Mammography with supplementary ultrasound showed higher accuracy, higher specificity, and lower recall rate in comparison with mammography with AI and in comparison with mammography with both ultrasound and AI. CLINICAL IMPACT. The findings fail to show benefit of AI with respect to screening mammography performed with supplementary breast ultrasound in patients with dense breasts.