194 research outputs found
A Comparison of Korean National Health Insurance Claims Database and Spontaneous Reporting System Database
학위논문(석사) -- 서울대학교대학원 : 약학대학 약학과, 2021.8. 홍송희.자발적부작용보고 시스템 (spontaneous reporting systems, SRS)에 비해 국민건강보험공단 청구자료 (HIRA)는 모든 피보험자의 진단 및 처방 정보가 포함되어 있지만, 약물 안전 감시에 적용되는 경우가 많이 없었다. 본 연구의 목적은 건강보험청구자료 (HIRA)와 자발적부작용보고자료 (KAERS)를 이용하여 항우울제 사용으로 인한 실마리정보를 탐색하고, 두 시스템에서 발견한 실마리정보의 특징을 비교하는 것이다.
본 연구에 사용된 자료는 2017년 HIRA와 KAERS 데이터이다. HIRA데이터의 경우는 실마리정보를 탐색하기 전에 모든 약물과 약물이상반응 (ADR)을 후향적 페어링하고 약물-이상반응 조합 (drug-ADR pair)을 추출했다. 두 시스템의 약물-이상반응 조합에 대하여 여러 가지 실마리정보 지표를 계산한 뒤 실마리정보의 중류 (class), 부작용일반성지표 (common ADR coverage, CAC)또는 허가상항내재지표 (labeling information coverage, LIC)측면에서 두 시스템을 비교 분석해 보았다. 부작용일반성지표는 흔한 ADR의 비율로 측정하고 허가상항내재지표는 mAP (Mean Average Precision)로 측정했다. 또한, 제약회사의 제품설명서 및 허가사항에 포함되지 않은 실마리정보는 protopathic bias평가또는 RR (Relative risk)평가로 확인되었다. Protopathic bias평가할때 LEOPARD (Observational Profiles of Adverse Events Related to Drug)를 이용했다. 그리고 성별, 나이, 시간대에 따라 실마리정보 분포의 변화를 관측하였다.
KAERS 데이터베이스에서 총 5,992건의 약물-이상반응 조합을 이용하여 총 51개 실마리정보를 발견했다. 제약회사의 제품설명서 및 허가사항에 포함되지 않은 실마리정보는 없었다. HIRA 데이터베이스에서 총 108,570건의 약물-이상반응 조합 만들어 총 62개 실마리정보를 발견했다. 이 중 5개는 제약회사의 제품설명서 및 허가사항에 포함되지 않은 실마리정보였다. KAERS에서 항우울제가 더 많은 장기 시스템의 장애와 관련이 있음을 보였다. KAERS에서 더 높은 mAP (EB05의 mAP : 1.00 [K] VS. 0.983 [H])를 보였지만 일반적인 부작용과 관련된 실마리정보는 HIRA보다 더 많이 발견되었다 (68.63 % [K] VS. 29.03 % [H]). 실마리정보를 확인할 때 LEOPARD를 통해 duloxetine과 myelopathy의 조합은 protopathic bias때문에 생기는 것으로 확인되었다 (P-value=0.01026). 각 연령 및 성별 그룹에서 실마리정보 탐색시 HIRA는 항상 KAERS보다 낮은 CAC와 LIC를 보였다. HIRA에서 시간대가 단축함에 따라 CAC는 감소하고 (29.03%, 27.87%, 27.27%) LIC는 증가했다 (0.983, 1.0, 1.0).
본 연구를 통해 실마리정보 탐색할 때 건강보험청구자료와 자발적부작용보고자료에서 발견한 실마리정보는 서로 다른 프로파일을 보였다. 건강보험청구자료를 통해 허가사항에 포함되지 않은 실마리정보를 발견되었으며 추가 연구를 통해 확인해야 한다. 앞으로 약물감시 업무에서 실마리정보 탐색 시 HIRA같은 건강보험청구자료를 더 많이 적용해야 할 것이다.Background: The spontaneous reporting system (SRS), such as the Korea Adverse Event Reporting System (KAERS), has a limitation in detecting all safety signals because the reports do not come from all drug uses. On the other hand, the claims data of the Korean National Health Insurance Review & Assessment (HIRA) has information on drug-induced conditions for all insurance-covered patients along with their prior prescription records, which helps investigate the temporal association between drugs and adverse drug reactions (ADRs). Therefore, complementing the HIRA to KAERS for drug safety signal detection would generate a more substantial list of safety signals than KAERS alone. This study has the following objectives: 1) compare the profiles of the signals (signal classes, common ADR coverage (CAC), and labeling information coverage (LIC)) detected in HIRA and KAERS databases; 2) verify the validity of the signals detected but not covered by the labeling information with protopathic bias evaluation and relative risk (RR) assessment; 3) determine whether the signal profile depends on demographics (age and gender) and different time windows (4, 8, 12 weeks) used to define the prior drug exposure.
Methods: ADR signal detection on the KAERS and HIRA databases (1st January 2017 to 31st December 2017) was conducted with Bayesian and non-Bayesian methods. The signal classes were constructed based on System Organ Class (SOC) as well as types of antidepressants. CAC was computed as the proportion of common ADRs among all the signals detected. LIC was represented by the mean average precision (mAP). Protopathic bias was controlled using Longitudinal Evaluation of Observational Profiles of Adverse Events Related to Drugs (LEOPARD). RR for each drug-ADR combination was based on prescription drug events and follow-up of ADR conditions.
Results: The numbers of signals detected in the KAERS and HIRA databases were 51 and 62, respectively. Most of the signals detected in KAERS consisted of autonomic nervous system disorders of SOC (N=17, 33.3%) and TCA (N=21, 41.2%) antidepressants while those in HIRA consisted of central & peripheral nervous system disorders of SOC (N=31, 50%) and SSRI (N=22, 35.5%) antidepressants. HIRA had 5 of the signals detected that are not found in the drug labeling information while KAERS had 0. The signals detected from KAERS had a higher CAC (68.63% [K] VS. 29.03% [H]) as well as a higher LIC (mAP for EB05: 1.00 [K] VS. 0.983 [H]) than those from HIRA. The unlabeled signal of myelopathy on duloxetine was a protopathic bias (P-value = 0.01026). Three of the four unlabeled signals did not show a statistically significant association between drug events and ADRs (lower bound of RR < 1). As for demographic subgroups, HIRA always showed lower CACs and LICs than KAERS. As for different time windows of drug-ADR pairing in HIRA, CACs decreased (29.03%, 27.87%, 27.27%) with a narrower window while LICs increasing (0.983, 1.0, 1.0).
Conclusion: The safety signals detected for antidepressants in HIRA (healthcare claims database) and KAERS (SRS) databases exhibited different signal profiles. The signals detected but not covered by drug labeling information, which were only detected in HIRA, need to be verified with further research. Safety signal detection in both healthcare claims and SRS databases would provide additional regulatory insight for pharmacovigilance.1. Introduction 1
1.1 Pharmacovigilance (PV) and safety signal detection around the world 1
1.1.1 Spontaneous reporting system (SRS) 1
1.1.2 Prescription–Event Monitoring (PEM) system 3
1.1.3 Observational Health Data Sciences and Informatics (OHDSI) 3
1.1.4 Healthcare databases 4
1.2 Pharmacovigilance (PV) in South Korea 6
1.2.1 Korea Adverse Event Reporting System (KAERS) 6
1.2.2 Re-examination System & Re-evaluation System 7
1.2.3 Claims data of Korean National Health Insurance Review & Assessment (HIRA) 7
1.3 Adverse effects of Antidepressants 9
1.3.1 Tricyclic antidepressants, Monoamine oxidase inhibitors (MAOIs) 9
1.3.2 Tricyclic antidepressants (TCAs) 9
1.3.3 Selective serotonin reuptake inhibitors (SSRIs) 10
1.3.4 Serotonin-norepinephrine reuptake inhibitors (SNRIs) 11
1.3.5 Other antidepressants 12
1.4 Objectives 13
2. Methods 14
2.1 Signal detection and comparison 14
2.1.1 KAERS 14
2.1.2 HIRA 16
2.1.3 Comparison of the signals detected in the two systems 18
2.2 Validity of the unlabeled signals detected in HIRA 20
2.2.1 Protopathic bias evaluation 20
2.2.2 Relative risk (RR) and the confidence interval 20
2.3 Demographics and time windows 22
3. Results 23
3.1 Signal detected and comparison between KAERS and HIRA 23
3.1.1 KAERS 23
3.1.2 HIRA 29
3.1.3 Comparison 36
3.2 Verification of the signals detected 41
3.2.1 Protopathic bias evaluation 41
3.2.2 Relative risk (RR) 42
3.3 Signal profiles change depending on demographics and time windows 44
5. Discussion 46
5.1 Signals detected 46
5.2 Comparison between HIRA and KAERS 47
5.3 Validity of the unlabeled signals 50
5.4 Gender differences 52
5.5 Limitations 53
6. Conclusion 54
7. Appendix 55
Appendix 1. Formulas for Bayesian methods 55
Appendix 2. Main ingredient codes in HIRA-NPS 58
Appendix 3. Identified ADRs in HIRA-NPS 59
Appendix 4. Stratified analysis for KAERS 62
Appendix 5. Stratified analysis for HIRA 67
Appendix 6. Signal detection with different time windows 71
8. References 74
Acknowledgements 74
국문 초록 81석
The Impact of Personal Remittances, FDI and Exports on Economic Growth: Evidence from West Africa
The study delves into West African data to assess the impact of personal remittances, FDI and exports on economic growth by applying panel data methodologies on 15 countries from 1991 to 2017. The study further applied panel fully modified ordinary least square, robust least square, and generalized linear model regression methodologies to make a statistical inference. From the results, it could be ascertained that personal remittances and exports have a strong and positive impact on economic growth. Meanwhile, FDI has a positive impact on economic growth as an individual factor, but with the existence of personal remittances and exports, FDI tends to become negative and significant in West Africa. The study proposes further studies into the area of FDI to unravel the exact relationship it has with economic growth. Keywords: Personal remittances, Foreign direct investment, Exports, Robust least squares, Fully modified ordinary least squares, Generalized linear model DOI: 10.7176/EJBM/11-23-04 Publication date: August 31st 201
MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer
<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.</p> <p>Results</p> <p>Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.</p> <p>Conclusions</p> <p>Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.</p
Translating features of military film titles from English into Russian
В данной статье рассматриваются особенности перевода названий военных фильмов с английского языка на русский. В ней рассматриваются проблемы и нюансы языковых и культурных различий между двумя языками, а также то, как эти факторы влияют на процесс перевода. В статье представлены особенности перевода фильмов военного жанра. Также дается ценная информация о сложной и запутанной природе перевода названий военных фильмов с английского языка на русский.This article discusses the translating features of war film titles from English into Russian. It explores the challenges and nuances of linguistic and cultural differences between the two languages and how these factors influence the translation process. The article also presents the features of translation of films of the military genre. Ultimately, this study provides valuable insight into the complex and intricate nature of translating war movie titles from English into Russian
A Journey to the West: The Ancient Dispersal of Rice Out of East Asia.
Funder: Max Planck Institute for the Science of Human HistoryRice is one of the most culturally valued and widely grown crops in the world today, and extensive research over the past decade has clarified much of the narrative of its domestication and early spread across East and South Asia. However, the timing and routes of its dispersal into West Asia and Europe, through which rice eventually became an important ingredient in global cuisines, has remained less clear. In this article, we discuss the piecemeal, but growing, archaeobotanical data for rice in West Asia. We also integrate written sources, linguistic data, and ethnohistoric analogies, in order to better understand the adoption of rice outside its regions of origin. The human-mediated westward spread of rice proceeded gradually, while its social standing and culinary uses repeatedly changing over time and place. Rice was present in West Asia and Europe by the tail end of the first millennium BC, but did not become a significant crop in West Asia until the past few centuries. Complementary historical, linguistic, and archaeobotanical data illustrate two separate and roughly contemporaneous routes of westward dispersal, one along the South Asian coast and the other through Silk Road trade. By better understanding the adoption of this water-demanding crop in the arid regions of West Asia, we explore an important chapter in human adaptation and agricultural decision making
Long Noncoding RNA HOXA-AS2 Promotes Papillary Thyroid Cancer Progression by Regulating miR-520c-3p/S100A4 Pathway
Background/Aims: Thyroid cancer is one of the most prevalent endocrine tumors. The present study examined the effects of lncRNA HOXA cluster antisense RNA2 (HOXA-AS2) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms. Methods: Quantitative real-time PCR was used to detect HOXA-AS2, miR-520c-3p and S100 calcium-binding protein A4 (S100A4) expression. Furthermore, the effects of HOXA-AS2 silencing and overexpression on cell proliferation, migration, and invasion were assessed in PTC in vitro by CCK8 and transwell assay. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in PTC. Results: We observed that HOXA-AS2 was up-regulated in PTC tissues. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited cell growth in PTC in vitro and in vivo. Further functional assays indicated that HOXA-AS2 significantly promoted PTC cell migration and invasion by promoting EMT. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in PTC cells. MiR-520c-3p was down-regulated in PTC tissues, and S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay. Conclusion: In summary, our results suggested that the HOXA-AS2/miR-520c-3p/S100A4 axis may play an important role in the regulation of PTC progression, which provides us with new insights into understanding the PTC
Compound K Inhibits Autophagy-Mediated Apoptosis Through Activation of the PI3K-Akt Signaling Pathway Thus Protecting Against Ischemia/Reperfusion Injury
Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury
A multi-wavelength mid-IR laser based on BaGa4Se7 optical parametric oscillators
A multi-wavelength mid-IR laser consisting of 3.05 μm, 4.25 μm, and 5.47 μm BaGa4Se7(BGSe)optical parametric oscillators (OPOs) switched by DKDP electro-optic switches with one 10 Hz/7.6 ns pumping wave is demonstrated. Maximum energies at 3.05 μm, 4.25 μm, and 5.47 μm are 1.35 mJ, 1.03 mJ, and 0.56 mJ, respectively, corresponding to optical-to-optical conversion efficiencies of 9.4%, 7.6%, and 4.2%. To the best of our knowledge, this study is the first of generation of three mid-IR wavelength lasers using electro-optic switches. Furthermore, this study provides a viable solution for a high-energy or high-power, compact, or even portable multi-wavelength mid-IR laser device that employs a single pumping wave
Digital Life Project: Autonomous 3D Characters with Social Intelligence
In this work, we present Digital Life Project, a framework utilizing language
as the universal medium to build autonomous 3D characters, who are capable of
engaging in social interactions and expressing with articulated body motions,
thereby simulating life in a digital environment. Our framework comprises two
primary components: 1) SocioMind: a meticulously crafted digital brain that
models personalities with systematic few-shot exemplars, incorporates a
reflection process based on psychology principles, and emulates autonomy by
initiating dialogue topics; 2) MoMat-MoGen: a text-driven motion synthesis
paradigm for controlling the character's digital body. It integrates motion
matching, a proven industry technique to ensure motion quality, with
cutting-edge advancements in motion generation for diversity. Extensive
experiments demonstrate that each module achieves state-of-the-art performance
in its respective domain. Collectively, they enable virtual characters to
initiate and sustain dialogues autonomously, while evolving their
socio-psychological states. Concurrently, these characters can perform
contextually relevant bodily movements. Additionally, a motion captioning
module further allows the virtual character to recognize and appropriately
respond to human players' actions. Homepage: https://digital-life-project.com/Comment: Homepage: https://digital-life-project.com
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