Letteratura scientifica selezionata sul tema "Koiwa Library"

Financial Accounting Standards for Micro, Small and Medium Entities (SAK EMKM) have been stipulated by Law Number 20 of 2008 as a standard in the preparation of financial reports for Micro, Small and Medium Enterprises (MSMEs). applied in the financial statements of the MSME Koica Milk Shop, Air Duku Village, Selupu Rejang District. The method used in this research is descriptive qualitative method and data collection techniques are carried out using library research techniques and field studies. The data used are primary data and secondary data. Based on the data obtained, the authors found the problem is that the financial statements have not been prepared. The company only records incoming milk so that it only produces daily recap data. The results of this study indicate the preparation of financial statements at the MSME Koica Milk Shop, Air Duku Village, Selupu Rejang District which consists of a statement of financial position, income statement and notes to financial statements. The author suggests that the company should immediately implement the financial statements that the author has made based on SAK EMKM in order to assist in future decision making.

Objective: Kyrgyzstan, located in Central Asia, is a country which has a strong will to achieve national development. The aim of this study is to measure the levels of trust of local residents, a highly important factor in national development, and to derive suggestions for improving it. To this end, the primary means employed is to target the residents of Kyrgyzstan and measure the levels of trust they have towards each other. Methods: The study uses data relating to aid projects for rural development that Korea’s Good Neighbors International organization (GNI) is jointly carrying out in Kyrgyzstan along with the Korea International Cooperation Agency (KOICA), a Korean aid provider. In order to carry out the aid project to Kyrgyzstan, these organizations conducted a baseline survey at the initial stage, and the results of this study were used for analysis. As regards the analytical method used in this study, neural network analysis was employed for the questionnaire survey data of 583 people in Kyrgyzstan that was used for the baseline survey. Results: Neural network analysis, a component of the big data analysis method, has recently been in the academic limelight. The analysis revealed that ethnicity had the greatest influence on the trust levels of Kyrgyzstan residents, followed by gender and education level, in that order. Conclusions: From this, it can be seen that multifaceted efforts are needed to increase the levels of trust of peoples other than ethnic Kyrgyzstanis, as they occupy a central position in Kyrgyzstan.

Background:Conventional observational studies have identified serum urate (SU) as an independent risk factor for cardiovascular diseases (CVDs),1,2but the causal relationships remain unsettled, with potential confounding and reverse causality. When applied correctly, Mendelian randomization (MR) employing genetic variants as instrumental variables can eliminate these biases and allow for causal inference.Objectives:To conduct a systematic review and meta-analysis of English-language, peer-reviewed MR studies on the causal effects of SU on CVDs and assess validation of key MR assumptions.Methods:A research librarian conducted a search (inception to January 2020) of four databases (Medline, Embase, Cochrane Library, and Web of Science), which was supplemented by hand-search. Titles and abstracts were screened by two independent reviewers, who subsequently evaluated and extracted data from full-text of selected articles. Pooled meta-analysis was performed using random-effects weighting.Results:Of 1014 articles identified, 40 were selected for full-text review and 13 studies reporting on CVDs were included in the systematic review (Figure 1). The first was published in 2009 and five were published in 2018 or 2019 alone. The included studies were of varying quality in regards to satisfying the assumptions for MR design.Fig. 1: PRISMA flow diagram.Overall, there was little evidence for a causal association between SU and risk of CVDs (Table 1). Random-effects meta-analysis revealed that SU was not significantly associated with risk of CVDs (OR=1.04; 95% CI=0.99-1.09) (Figure 2). 11 of the 13 studies reported null estimates for the effects of genetically-determined SU levels on CVDs. Two studies with small numbers of cases (N=125 and 222) reported significant associations, but these pertained to highly-specific subgroups.Table 1.Summary of included studies. CAD: Coronary Artery Disease; CHD: Coronary Heart Disease; IHD: Ischaemic heart disease; MI: Myocardial Infarction; MR: Mendelian Randomization; PVD: Peripheral Vascular Disease; SNP: Single Nucleotide PolymorphismFirst author; yearNumber of SNPs analyzedOutcome(n cases)PowerMR criteria validated:1. relevance2. pleiotropy3. confoundingConclusionStark; 200910 separatelyCAD (1,473)30%-66%1, 3NullYang; 20108 combinedCHD (3,050)<80%1, 2, 3NullPalmer; 20131 (rs7442295)IHD (3,742)N/A1, 2*, 3NullKleber; 20158 combinedCAD (2,418)PVD (295)N/A1, 2, 3NullHan; 20152 separatelyCHD (1,146)80%1, 2*, 3NullTesta; 20151 (rs734553)CVD events (CVD death, stroke, MI) (222)N/A1, 2*Significant for CV eventsWhite; 201631 combinedCAD (65,877)83%1, 2, 3NullKeenan; 201614 combinedCHD (54,501)Stroke (14,779)>80%1, 2, 3NullLi; 201831 combinedIHD (9,467)MI (3,625)70%1, 2, 3NullLi; 201931 combinedCHD (60,801)MI (43,676)Stroke (10,307)N/A1, 2, 3NullMacias-Kauffer; 20192 separatelyCAD (704)N/A1, 2*, 3NullEfstathiadou; 201928 separatelyCHD (184,305)MI (54,162) Stroke (514,791)>80%1, 2, 3NullChiang; 20198 combinedCHD (125)Stroke (57)N/A1, 2, 3Significant for CHD* Risk of pleiotropy (assumption 2) is low when utilizing few well-established SNPsFig. 2: Pooled meta-analysis results.Conclusion:Evidence from this systematic review does not support a causal role for SU levels and CVDs. As such, interventions targeting SU levels alone are unlikely to lower the risk of CVDs.References:[1] Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 2012;125:679-87 e1.[2] Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007;116:894-900Disclosure of Interests:Jeewoong Choi: None declared, Natalie McCormick: None declared, Shelby Marozoff: None declared, Mary De Vera: None declared, Hyon Choi Grant/research support from: Ironwood, Horizon, Consultant of: Takeda, Selecta, Horizon, Kowa, Vaxart, Ironwood

Abstract Graft-versus-host-disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent complication and one of the major causes of non-relapse mortality. However, its pathogenesis has not yet been fully understood. We cloned signal-transducing adaptor protein (STAP)-2 as a c-fms binding protein from a fetal liver library in 2003. The family that contains STAP-1 and STAP-2 has a pleckstrin homology (PH) and Src-homology 2 (SH2)-like domains, suggesting that this adapter protein functions as an immune and inflammatory regulator. Indeed, STAP-2 regulates adhesion and chemotaxis in T cells (Sekine et al., J Immunol. 2009). In this study, we aimed to elucidate the roles of STAP family in GVHD. First, we examined the expression of STAP-1 and STAP-2 mRNA in various human hematopoietic subsets, including CD34+ CD38- hematopoietic stem cells (HSCs), CD34+ CD38+ hematopoietic progenitor cells (HPCs), CD19+ CD27- naïve B cells, CD19+ CD27+ memory B cells, CD3+ CD4+ helper T-cells, and CD3+ CD8+ cytotoxic T lymphocytes, using real-time PCR. As a result, STAP-1 and STAP-2 were expressed in lymphoid cells, as well as HSCs and HPCs. STAP-2 mRNA was highly expressed in T cells. Next, to investigate the role of STAPs in GVHD, we made an experimental murine model. To study the pathogenesis of immune reconstitution and tolerance after allo-HSCT, lethally irradiated BALB/c mice were injected with T and B cell-depleted bone marrow cells (5×106 cells) derived from syngeneic BALB/c or allogeneic C57BL/6 mice on day 0. Co-transplantation of splenocytes was not adapted in this model. Survival and clinical degree of GVHD were assessed by a scoring system that sums changes in 5 clinical parameters: body weight (BW) loss, posture, activity, fur texture, and skin integrity. Recipients transplanted from allogenic wild type (WT) C57BL/6 donor survived without suffering from severe GVHD symptoms, owing to development of immune tolerance against allogeneic antigens. However, compared to syngeneic transplanted mice, these recipients started to show gradual BW loss and GVHD score was increased approximately 28 days after allo-HSCT, indicating the existence of an allogeneic immune reaction. To evaluate the role of STAPs in GVHD, we generated transgenic mice (Tg) that overexpress STAP under the control of Em enhancer and Lck proximal promoter. The promoter could drive expression of the inserted cDNA in lymphoid lineage cells from the common lymphoid progenitor (CLP) stage. When STAP-2 Tg marrow was used as a donor source, we found that the overall survival of STAP-2 Tg recipients was significantly lower than that of WT recipients (22.2% and 91.7%, respectively; p<0.001) on day 60. STAP-2 Tg recipients showed decreased BW and had a higher clinical GVHD score with statistical significance compared to control WT recipients. The overexpression of STAP-1 also exacerbated the severity of GVHD. At day 42, BW was decreased by 16.3% in WT recipients. In contrast, recipients of STAP-1 Tg and the STAP-2 Tg donor showed more severe BW loss along with diarrhea (23.3% and 29.8%, respectively). STAP-1 as well as STAP-2 Tg recipients showed significantly worsened GVHD scores, and this lasted until day 90 at the end of follow-up. In histologic examination of both STAP Tg recipients, inflammatory damages with lymphocyte infiltration were most notably observed in the colon. Interestingly, we found that thymus was atrophic or indistinguishable and the cortico-medullary junction disappeared. Moreover, compared to control WT recipients, the number of CD4+ CD25+ regulatory T (Treg) cells in the peripheral blood was significantly low in STAP-2 Tg recipients on day 60 (WT vs STAP-2 Tg; 44.0 /μL vs 18.2 /μL; p<0.05). In this study, we show that STAPs in reconstituted lymphocytes after allo-HSCT regulate the pathogenesis of GVHD. Our results suggest that STAP activation in lymphocytes during immune reconstitution accelerates gut and thymic GVHD. Severe thymic damage induced by STAP overexpression might contribute to impairment of immune tolerance such as a decreased number of Treg cells as well as dysfunction of thymic negative selection of host-reactive T cells after allo-HSCT, which is involved in persistence of GVHD. Future study should further elucidate the detailed molecular mechanisms involved. Disclosures Ichii: Celgene K.K.: Speakers Bureau; Kowa Pharmaceutical Co.,LTD.: Speakers Bureau; Novartis Pharma K.K.: Speakers Bureau. Shibayama:Takeda Pharmaceutical Co.,LTD.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Jansen Pharmaceutical K.K: Honoraria; Ono Pharmaceutical Co.,LTD: Honoraria, Research Funding; Fujimoto Pharmaceutical: Honoraria, Research Funding; Novartis Pharma K.K.: Honoraria, Research Funding; Bristol-Meyer Squibb K.K: Honoraria, Research Funding; Celgene K.K.: Honoraria, Research Funding. Oritani:Novartis Pharma: Speakers Bureau. Kanakura:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Abstract Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder caused by hematopoietic stem cells expressing the BCR-ABL fusion oncoprotein, which constitutively activates multiple signal transduction pathways such as mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt, and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Although tyrosine kinase inhibitor (TKI) therapy results in dramatic clinical success, studies have shown that TKIs are unable to eradicate leukemic stem cells (LSCs). Several key signaling molecules and pathways have been proposed to regulate the survival of CML LSCs in the presence of TKI; however, the details remain unclear. It is necessary to elucidate the mechanisms that maintain LSCs to better understand the pathogenesis of CML and develop new treatment approaches. The family of signal-transducing adaptor proteins (STAPs), which includes STAP-1 and STAP-2, has been implicated in various intracellular signaling pathways. In 2003, we cloned STAP-2 as a c-fms interacting protein and reported that STAP-2 binds to BCR-ABL and enhances activity, leading to the activation of downstream molecules such as ERK, STAT5, BCL-xL, and BCL2. STAP-1 was cloned as a c-kit interacting protein from a hematopoietic stem cell library, but it is unknown whether STAP-1 plays a role in CML. Given the structural homology between STAP-1 and STAP-2 and the hematopoietic expression of STAP-1, we hypothesized that STAP-1 might contribute to the leukemogenesis of CML. A STAP-1-deficient (KO) CML mouse model was developed. To generate this model, lineage (Lin)− Sca-1+ c-Kithigh (LSK) fraction isolated from bone marrow (BM) cells was infected with a retrovirus carrying BCR-ABL1 and GFP and subsequently transplanted into congeneric recipients. STAP-1 KO CML mice showed significantly longer survival than WT CML mice and displayed less severe splenomegaly and lung hemorrhages compared with WT mice. In recipient BM, absolute numbers of STAP-1 KO LSCs (GFP+ LSK cells) were significantly lower than WT LSCs. In the colony-forming assay, STAP-1 KO LSCs generated fewer colonies compared to WT LSCs. Using flow cytometric analysis, we found that STAP-1 KO LSCs had a higher apoptotic rate than WT LSCs. These findings suggest that the suppression of apoptosis induced by STAP-1 mediates longer survival of LSCs. To further understand the effects of STAP-1, we performed a gene expression analysis using RNA-sequence (RNA-seq) and compared WT and STAP-1 KO CML LSCs. When canonical pathways were analyzed with Ingenuity Pathway Analysis, various pathways associated with inflammatory cytokines were observed to be regulated in STAP-1 KO CML LSCs. Changes in mRNA expression, including that of SOS1, SOS2, FOXO3, FASLG, NFKB2, and BCL-xL, indicated that the PTEN signaling pathway, known to play a tumor suppressive role in CML, was significantly activated by STAP-1 KO (p=1.096E-3, activation Z-score=2.611). The pathway related to JAK/STAT signaling was also affected (p=2.04E-5, activation Z-score=-3.286). Downstream genes in the JAK/STAT signaling pathway, such as STAT5B and BCL-xL, were downregulated more than 2-fold in STAP-1 KO LSCs, suggesting that the deletion of STAP-1 inhibits the expression of STAT5-targeted anti-apoptotic protein and induced apoptosis of CML LSCs. To confirm the results of the RNA-seq experiment, an intracellular flow cytometric assay with CML Lin− cells was conducted. The frequency of cells positive for phosphorylated STAT5 was reduced for STAP-1 KO compared with that for WT. Quantitative PCR with CML LSCs confirmed the downregulation of BCL2 and BCL-xL, which are STAT5-targeted anti-apoptotic genes, in STAP-1 KO CML LSCs. In conclusion, we show that STAP-1 plays a crucial role in the maintenance of CML LSCs using a murine model of CML. STAP-1 deficiency results in the reduction of phosphorylated STAT5, downregulation of anti-apoptotic genes BCL-2 and BCL-xL, and induced apoptosis of CML LSCs. These findings suggest that STAP-1 and related signaling pathways could be potential therapeutic targets for CML LSCs. Disclosures Ichii: Celgene K.K.: Speakers Bureau; Kowa Pharmaceutical Co.,LTD.: Speakers Bureau; Novartis Pharma K.K.: Speakers Bureau. Shibayama:Fujimoto Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical Co.,LTD.: Honoraria, Research Funding; Celgene K.K.: Honoraria, Research Funding; Jansen Pharmaceutical K.K: Honoraria; Ono Pharmaceutical Co.,LTD: Honoraria, Research Funding; Novartis Pharma K.K.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Bristol-Meyer Squibb K.K: Honoraria, Research Funding. Oritani:Novartis Pharma: Speakers Bureau. Kanakura:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.