ABSTRACT
Methane is a significant greenhouse gas (GHG), and it is imperative to understand its spatiotemporal distribution and primary sources in areas with higher methane concentrations, as such insights are essential for informing effective mitigation policies. In this study, we employed TROPOMI satellite retrievals to analyze the spatiotemporal patterns of methane distributions and identify major emission sources in South Korea over the period from August 2018 to July 2019. Additionally, we examined the spatial correlations between satellite methane retrievals and emission sources to characterize regions with higher methane levels on an annual basis.Concerning spatial distributions, concentrations exceeding 1870 ppb were predominantly observed in western non-mountainous regions, particularly in rice paddy areas. Moreover, sporadic concentrations exceeding 1880 ppb were detected in large ports and industrial zones, primarily located in coastal regions of South Korea.Our spatial correlation analysis, conducted using the SDMSelect method, identified specific emissions contributing to regions with higher methane concentrations. There were some areas with relatively strong correlations between high XCH4 and emissions from the domestic livestock industry, fossil fuel utilization (specifically, the oil and gas sector), landfills, and rice paddies. This analysis, incorporating domestic emission inventories and satellite data, provides valuable insights into the characteristics of regional methane concentrations. In addition, this analysis can assess national methane emissions inventories, where there is limited information on the spatial distributions, offering critical information for the prioritization of domestic regional policies aimed at reducing greenhouse gas emissions.
Subject(s)
Greenhouse Gases , Oryza , Environmental Monitoring , Fossil Fuels , Methane , Republic of KoreaABSTRACT
Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems.
Subject(s)
Anti-Bacterial Agents , Developing Countries , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Drug Resistance, Bacterial , Asia/epidemiologyABSTRACT
BACKGROUND: Endoscopic submucosal dissection has technical limitations for the resection of gastric epithelial tumors with severe fibrosis and mixed or exophytic gastric subepithelial tumors (SETs). AIMS: To analyze the safety and effectiveness of endoscopic subserosal dissection (ESSD) for tumors growing in the subserosal space. METHODS: This observation study enrolled 18 patients who were diagnosed with gastric tumors and underwent ESSD at the Presbyterian Medical Center from 2010 to March 2019. RESULTS: A total of 18 patients were treated by ESSD. The mean age of the patients was 61.7 years. The mean length of the long axis of the tumor was 18.0 ± 5.0 mm. The mean operation time was 44 (range 11-167) min. The pathologic diagnosis was leiomyoma in nine cases (50.0%), gastrointestinal stromal tumor in six (33.3%), low-grade adenoma with severe fibrosis in two (11.1%), and schwannoma in one (5.6%). There were three cases of perforation, which were treated conservatively. The complete resection rate was 94%, and local or systemic tumor recurrence was not seen in a mean 70 months of follow-up. CONCLUSION: ESSD can be used for epithelial tumors with severe fibrosis and mixed or exophytic gastric SETs in the lesser curvature, cardia, or fundus that cannot be treated using standard methods.
Subject(s)
Endoscopic Mucosal Resection , Gastrointestinal Stromal Tumors , Neoplasms, Glandular and Epithelial , Stomach Neoplasms , Humans , Middle Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Gastroscopy/methods , Neoplasm Recurrence, Local/pathology , Endoscopic Mucosal Resection/methods , Gastrointestinal Stromal Tumors/surgery , Neoplasms, Glandular and Epithelial/pathology , Fibrosis , Treatment Outcome , Gastric Mucosa/surgery , Retrospective StudiesABSTRACT
Downregulation of claudin 1, a critical tight junction protein, has been correlated with increased invasiveness in breast cancer. However, recent studies suggest that claudin 1 contributes to the progression of some molecular subtypes of breast cancer. In this study, claudin 1 promotes migration in luminal-like MCF7 human breast cancer cells and increases their sensitivity to tamoxifen, etoposide, and cisplatin. We also observed an inverse relationship between upregulation of claudin 1 and TGFß. Collectively, our results suggest that claudin 1 has the potential to be used as a predictive marker for treatment efficacy for specific breast cancer patient subgroups.
ABSTRACT
Downregulation of claudin 1, a critical tight junction protein, has been correlated with increased invasiveness in breast cancer. However, recent studies suggest that claudin 1 contributes to the progression of some molecular subtypes of breast cancer. In this study, claudin 1 promotes migration in luminal-like MCF7 human breast cancer cells and increases their sensitivity to tamoxifen, etoposide, and cisplatin. We also observed an inverse relationship between upregulation of claudin 1 and TGFß. Collectively, our results suggest that claudin 1 has the potential to be used as a predictive marker for treatment efficacy for specific breast cancer patient subgroups.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Movement/drug effects , Cell Movement/genetics , Claudin-1/genetics , Tamoxifen/pharmacology , Breast Neoplasms/genetics , Cell Line, Tumor , Cisplatin/pharmacology , Down-Regulation/drug effects , Down-Regulation/genetics , Etoposide/pharmacology , Female , Gene Expression/drug effects , Gene Expression/genetics , Humans , MCF-7 Cells , Tight Junctions/drug effects , Tight Junctions/genetics , Transforming Growth Factor beta/geneticsABSTRACT
The potential for pharmacodynamic (PD) biomarkers to improve the efficiency of biosimilar product development and regulatory approval formed the premise for the virtual workshop Pharmacodynamic Biomarkers for Biosimilar Development and Approval hosted by the US Food and Drug Administration (FDA) and Duke Margolis, September 2021. Although the possibility of PD biomarkers replacing the to-date routine comparative phase III confirmatory study currently expected by the FDA was discussed, the motivation and feasibility for biosimilar sponsors developing such markers and the regulatory risks entailed largely were not. Even more fundamental is the already established greater comparative value of the pharmacokinetic (PK) study as the most sensitive clinical assay for detecting subtle differences between two products. Consequently, the comparative analytical assessment and the head-to-head PKs will have already answered the core questions as to the biosimilarity of the candidate product to its reference. No further actionable information is obtained with either a PD study or a comparative clinical phase III study even as they may provide some reassurance of what is already known. When a suitable PD biomarker is available for the originator reference product they have already been used for biosimilar development. We must carefully consider the core requirements and timelines inherent in biosimilar development and how they occur in parallel rather than in the series we see for originator products. In order to improve the efficiency of biosimilar development, we need to ask the right questions based on a full understanding of how biosimilars have been developed to date and can be in the future.
Subject(s)
Biosimilar Pharmaceuticals , United States , Humans , Biosimilar Pharmaceuticals/pharmacokinetics , United States Food and Drug Administration , Forecasting , Drug ApprovalABSTRACT
Callus, a valuable tool in plant genetic engineering, originates from dedifferentiated cells. While transcriptional reprogramming during callus formation has been extensively studied in Arabidopsis thaliana, our knowledge of this process in other species, such as Glycine max, remains limited. To bridge this gap, our study focused on conducting a time-series transcriptome analysis of soybean callus cultured for various durations (0, 1, 7, 14, 28, and 42 days) on a callus induction medium following wounding with the attempt of identifying genes that play key roles during callus formation. As the result, we detected a total of 27,639 alterations in gene expression during callus formation, which could be categorized into eight distinct clusters. Gene ontology analysis revealed that genes associated with hormones, cell wall modification, and cell cycle underwent transcriptional reprogramming throughout callus formation. Furthermore, by scrutinizing the expression patterns of genes related to hormones, cell cycle, cell wall, and transcription factors, we discovered that auxin, cytokinin, and brassinosteroid signaling pathways activate genes involved in both root and shoot meristem development during callus formation. In summary, our transcriptome analysis provides significant insights into the molecular mechanisms governing callus formation in soybean. The information obtained from this study contributes to a deeper understanding of this intricate process and paves the way for further investigation in the field.
ABSTRACT
South Korea's population is declining and its composition changing, associated with lowest-low fertility rates and rapid aging (super aging). When estimating changes in future exposure to extreme heat events (EHE), events that are predicted to be intensified due to climate change, it is important to incorporate demographic dynamics. We analyze business-as-usual (BAU) population and climate scenarios-where BAU refers to no significant change in current processes and trends in either domain-from 2010 to 2060 for South Korea. Data for both BAU scenarios are spatially linked and used to measure and identify national and sub-national and age-group specific EHE exposure. The results reveal an increasing exposure to EHE over time at the national level, but this varies widely within the country, measured at the municipal level. The most intensive exposure levels will be in the decade ending in 2040 driven by high estimated severe EHE. Sub-nationally, Seoul will be the most vulnerable municipality associated with super aging, while severe EHE not demographic factors will be relevant in Daegu, the second-most vulnerable metropolitan area. By 2060, national estimates suggest the older population will be up to four times more exposed to EHE than today. While the population of South Korea will decline, the rapid aging of the population ensures that specific regions of the country will become exceedingly vulnerable to EHE.
ABSTRACT
Endoscopic resection is an effective treatment for subepithelial tumors arising from the muscularis propria layer of the stomach. However, the invasion pattern revealed by the pathological examination of tumor specimens is often not consistent with the findings of preprocedural endoscopic ultrasounds (EUS). We compared the real growing patterns of tumors, as evaluated on histopathological examination, with their EUS images, and analyzed the outcomes of endoscopic resections in relation to the EUS findings. From January 2006 to June 2015, 32 patients underwent endoscopic resection for gastric tumors originating from the muscularis propria at our hospital. We divided the patients into 3 groups according to the location of the tumor as diagnosed using pre procedural EUS: submucosa (group I, n = 5), muscularis propria (group II, n = 14), and tumors extending into the outer cavity (group III, n = 13). Histopathological examination revealed 15 patients with gastrointestinal stromal tumors (GISTs), 14 with leiomyomas, and 3 with schwannomas. Accuracy of EUS in evaluating tumor invasion was 56%. Some tumors in groups I and II was removed by endoscopic submucosal dissection only. Muscular dissection was needed in 10 patients (71%) in group II and 9 patients (69%) in group III. Four patients (31%) in group III were found to have subserosal tumors. The complete resection rate was 88% (23 patients) among patients who underwent endoscopic submucosal dissection and endoscopic muscular dissection, and 67% (4 patients) among patients who underwent endoscopic subserosal dissection (ESSD). The tumor was completely removed in 12 patients (86%) in group II and 10 patients (77%) in group III. EUS accurately predicts the layer of the subepithelial tumor in the stomach; however, the pattern of invasion of surrounding structures is difficult to evaluate using EUS.
Subject(s)
Endoscopic Mucosal Resection , Gastrointestinal Stromal Tumors , Stomach Neoplasms , Endoscopic Mucosal Resection/methods , Endosonography , Gastric Mucosa/diagnostic imaging , Gastric Mucosa/pathology , Gastric Mucosa/surgery , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Gastroscopy/methods , Humans , Retrospective Studies , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most.
Subject(s)
Biosimilar Pharmaceuticals , Biosimilar Pharmaceuticals/therapeutic use , Drug Approval , Humans , United States , United States Food and Drug AdministrationABSTRACT
SO2 column densities from Ozone Monitoring Instrument provide important information on emission trends and missing sources, but there are discrepancies between different retrieval products. We employ three Ozone Monitoring Instrument SO2 retrieval products (National Aeronautics and Space Administration (NASA) standard (SP), NASA prototype, and BIRA) to study the magnitude and trend of SO2 emissions. SO2 column densities from these retrievals are most consistent when viewing angles and solar zenith angles are small, suggesting more robust emission estimates in summer and at low latitudes. We then apply a hybrid 4D-Var/mass balance emission inversion to derive monthly SO2 emissions from the NASA SP and BIRA products. Compared to HTAPv2 emissions in 2010, both posterior emission estimates are lower in United States, India, and Southeast China, but show different changes of emissions in North China Plain. The discrepancies between monthly NASA and BIRA posterior emissions in 2010 are less than or equal to 17% in China and 34% in India. SO2 emissions increase from 2005 to 2016 by 35% (NASA)-48% (BIRA) in India, but decrease in China by 23% (NASA)-33% (BIRA) since 2008. Compared to in situ measurements, the posterior GEOS-Chem surface SO2 concentrations have reduced NMB in China, the United States, and India but not in South Korea in 2010. BIRA posteriors have better consistency with the annual growth rate of surface SO2 measurement in China and spatial variability of SO2 concentration in China, South Korea, and India, whereas NASA SP posteriors have better seasonality. These evaluations demonstrate the capability to recover SO2 emissions using Ozone Monitoring Instrument observations.
ABSTRACT
OBJECTIVE: Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. MATERIALS AND METHODS: We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. RESULTS: The median age was 55.5 years (range, 37-68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5-25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8-173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9-18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. CONCLUSION: Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.