Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis

Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis

Highly reliable GIGA-sized synthetic human therapeutic antibody library construction

BackgroundMonoclonal antibodies (mAbs) and their derivatives are the fastest expanding category of pharmaceuticals. Efficient screening and generation of appropriate therapeutic human antibodies are important and urgent issues in the field of medicine. The successful in vitro biopanning method for antibody screening largely depends on the highly diverse, reliable and humanized CDR library. To rapidly obtain potent human antibodies, we designed and constructed a highly diverse synthetic human single-chain variable fragment (scFv) antibody library greater than a giga in size by phage display. Herein, the novel TIM-3-neutralizing antibodies with immunomodulatory functions derived from this library serve as an example to demonstrate the library’s potential for biomedical applications.MethodsThe library was designed with high stability scaffolds and six complementarity determining regions (CDRs) tailored to mimic human composition. The engineered antibody sequences were optimized for codon usage and subjected to synthesis. The six CDRs with variable length CDR-H3s were individually subjected to β-lactamase selection and then recombined for library construction. Five therapeutic target antigens were used for human antibody generation via phage library biopanning. TIM-3 antibody activity was verified by immunoactivity assays.ResultsWe have designed and constructed a highly diverse synthetic human scFv library named DSyn-1 (DCB Synthetic-1) containing 2.5 × 1010 phage clones. Three selected TIM-3-recognizing antibodies DCBT3-4, DCBT3-19, and DCBT3-22 showed significant inhibition activity by TIM-3 reporter assays at nanomolar ranges and binding affinities in sub-nanomolar ranges. Furthermore, clone DCBT3-22 was exceptionally superior with good physicochemical property and a purity of more than 98% without aggregation.ConclusionThe promising results illustrate not only the potential of the DSyn-1 library for biomedical research applications, but also the therapeutic potential of the three novel fully human TIM-3-neutralizing antibodies

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan

Aims/Introduction To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. Materials and Methods In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. Results A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by −0.73% (95% confidence interval [CI] −0.80, −0.67), body weight was -1.61 kg (95% CI −1.79, −1.42), and systolic/diastolic blood pressure by −3.6/−1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (−0.82%) than switched therapy (−0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. Conclusions In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The Relationship between Runoff Coefficient and SCS Curve Number

At present, the rational formula is often applied to estimate the peak flow of watershed in Taiwan. The determination of runoff coefficient of rational formula is usually questionable by users because the range of runoff coefficient is so big and it is classified by slope as shown in the Technical Regulation for Soil and Water Conservation. Runoff coefficient will directly affect peak flow and thus will affect the decision of the engineering construction scale, so we have to do further investigate really and necessarily. In view of this, we will search some factors of hydrology (rainfall, runoff and etc.) and geography (landuse, soil texture and etc.) in Hou-long watershed, calculate the real runoff coefficient C, curve number CN, the estimating runoff coefficient C'' and curve number CN'' with the SCS method and try to find out the relationship among this four numbers. This result shows that the estimating runoff coefficients, C'', with SCS method are usually larger than the real ones, C. On the other hand, the real curve numbers, CN, are calculated by GIS technology and area weighting conception, and the estimating curve numbers, CN'', are estimated with rainfall and runoff records. To compare CN and CN'', CN'' is usually smaller than CN. Results of this study are as follows, in Hou-long watershed, the estimating runoff coefficients, C'', are about 0.90, and the real ones are between 0.76 and 0.82. Real average curve numbers, CN, in Pian-chou, Ta-lu-keng and Pei-shih-Bridge basin are 63.04, 61.82 and 61.83, and the estimating ones, CN'', are between 37.74 and 45.94.目前台灣對於集水區內洪峰逕流量之推估，常採用合理化公式，公式中有關逕流係數之選定，由於水土保持技術規範中逕流係數參考表之訂定範圍過大，且僅以坡度予以分類，常令使用者在選用時感到疑惑。由於逕流係數直接影響逕流量之推估，對於工程施做規模之決策影響甚鉅，實有必要進行深入研究。為此，本研究擬針對後龍溪流域內各種水文因子(降雨、逕流等)及地文因子(土地利用型態、土壤類別等)進行相關資料蒐集與調查，同時配合美國土壤保持局( The U. S. Soil Conservation Service, SCS ) 通用之曲線值( Curve Number, CN )法，求得實測及估測之逕流係數C、C'' 與實測及估測之曲線值CN、CN'' ，並試圖找出其間之相互關係。 由結果發現，利用SCS法推估之逕流係數C'' 多大於實測之逕流係數C，而逕流曲線值部份，根據GIS技術及面積加權概念所得之實際逕流曲線值CN，與利用降雨、逕流量推估之逕流曲線值CN'' 相比較，則CN'' 多小於CN。本研究結果數據顯示如下：後龍溪流域之推估逕流係數C'' 約為0.90，而實測逕流係數C則介於0.76至0.82之間。彼岸橋、打鹿坑及北勢大橋三集水分區之實際平均逕流曲線值CN分別為63.04、61.82及61.83；而推估平均逕流曲線值CN'' 則介於37.74至45.94間。目錄 摘要 I Abstract II 目錄 III 表目錄 IV 圖目錄 VI 第壹章 緒論 1 第一節 研究動機與目的 1 第貳章 前人研究與理論介紹 3 第一節 文獻回顧 3 第二節 地理資訊系統 5 第三節 合理化公式 5 第四節 SCS逕流曲線法 11 第參章 研究材料與方法 20 第一節 研究流程與步驟 20 第二節 試區概述 22 第三節 水文資料蒐集與整理 24 一、 雨量站資料 27 二、 流量站資料 37 第四節 地文資料蒐集與整理 41 一、 土壤質地分布圖 41 二、 土地利用分布圖 46 第肆章 結果與討論 52 第一節 各集水分區CN值分布情形 52 第二節 各集水分區之實測逕流係數及推估CN'' 值 58 一、 實測降雨量 58 二、 實測直接逕流量 62 三、 實測逕流係數與推估逕流曲線值CN'' 67 第三節 各集水分區之推估逕流係數 72 第四節 各集水分區之逕流係數及逕流曲線值比較 76 第伍章 結論與建議 80 第一節 結論 80 第二節 建議 81 參考文獻 82 表目錄 表1 - 1 逕流係數C值參考表 2 表2 - 1 台北市不同土地分區依其不透水性所定之逕流係數 8 表2 - 2 合理化公式之逕流係數 9 表2 - 3 逕流係數C值 10 表2 - 4 SCS法之土壤分類表 16 表2 - 5 SCS法之逕流曲線值表(Ia=0.2S) 17 表2 - 6 臨前水分條件分類表 18 表2 - 7 台灣地區土壤臨前水分條件分類表 18 表2 - 8 SCS法臨前水文條件之CN值對照表 19 表3 - 1 現有雨量站站況一覽表 26 表3 - 2 現有流量站站況一覽表 26 表3 - 3 和興雨量站西元1997~2006年間降雨量統計表 28 表3 - 4 橫龍山雨量站西元1997~2006年間降雨量統計表 29 表3 - 5 大湖(1)雨量站西元1997~2006年間降雨量統計表 30 表3 - 6 彼岸橋集水分區徐昇氏多邊形法雨量站控制面積比例表 34 表3 - 7 打鹿坑集水分區徐昇氏多邊形法雨量站控制面積比例表 35 表3 - 8 北勢大橋集水分區徐昇氏多邊形法雨量站控制面積比例表 36 表3 - 9 彼岸橋流量站西元1997~2005年間逕流量統計表 38 表3 - 10 打鹿坑流量站西元1997~2005年間逕流量統計表 39 表3 - 11 北勢大橋左岸流量站西元1997~2006年間逕流量統計表 40 表3 - 12 台灣土壤質地分類編號表 41 表3 - 13 台灣土壤質地分類與SCS土壤分類對照表 42 表3 - 14 彼岸橋集水分區土壤質地分布面積比例表 43 表3 - 15 打鹿坑集水分區土壤質地分布面積比例表 44 表3 - 16 北勢大橋集水分區土壤質地分布面積比例表 45 表3 - 17 土地利用分類代碼表 46 表3 - 18 本研究與水土保持局之土地利用分類對照表 47 表3 - 19 彼岸橋集水分區土地利用分布面積比例表 48 表3 - 20 打鹿坑集水分區土地利用分布面積比例表 49 表3 - 21 北勢大橋集水分區土地利用分布面積比例表 50 表3 - 22 本研究與SCS法之土地利用分類對照表 51 表3 - 23 本研究所合併之SCS CN值表 51 表4 - 1 彼岸橋集水分區CN值分布面積比例表(1) 55 表4 - 2 彼岸橋集水分區CN值分布面積比例表(2) 55 表4 - 3 打鹿坑集水分區CN值分布面積比例表(1) 56 表4 - 4 打鹿坑集水分區CN值分布面積比例表(2) 56 表4 - 5 北勢大橋集水分區CN值分布面積比例表(1) 57 表4 - 6 北勢大橋集水分區CN值分布面積比例表(2) 57 表4 - 7 彼岸橋集水分區西元1997~2006年間平均降雨量統計表 59 表4 - 8 打鹿坑集水分區西元1997~2006年間平均降雨量統計表 60 表4 - 9 北勢大橋集水分區西元1997~2006年間平均降雨量統計表 61 表4 - 10 彼岸橋流量站西元1997~2005年間豐水期直接逕流量統計表 63 表4 - 11 打鹿坑流量站西元1997~2005年間豐水期直接逕流量統計表 64 表4 - 12 北勢大橋左岸流量站西元1997~2006年間豐水期直接逕流量統計表 65 表4 - 13 三集水分區之豐水期總直接逕流量統計表 66 表4 - 14 彼岸橋集水分區西元1997~2005年間豐水期逕流係數統計表 69 表4 - 15 打鹿坑集水分區西元1997~2005年間豐水期逕流係數統計表 70 表4 - 16 北勢大橋集水分區西元1997~2006年間豐水期逕流係數統計表 71 表4 - 17 彼岸橋集水分區西元1997~2005年間豐水期推估逕流係數統計表 73 表4 - 18 打鹿坑集水分區西元1997~2005年間豐水期推估逕流係數統計表 74 表4 - 19 北勢大橋集水分區西元1997~2006年間豐水期推估逕流係數統計表 75 表4 - 20 彼岸橋集水分區西元1997~2005年間豐水期逕流係數與逕流曲線值比較表 77 表4 - 21 打鹿坑集水分區西元1997~2005年間豐水期逕流係數與逕流曲線值比較表 78 表4 - 22 北勢大橋集水分區西元1997~2006年間豐水期逕流係數與逕流曲線值比較表 79 圖目錄 圖2 - 1 初期降雨損失量Ia 、有效降雨總量Pe 以及入滲總量F 之關係圖 11 圖2 - 2 降雨量與逕流量累積曲線圖 12 圖2 - 3 SCS法有效降雨之計算 15 圖3 - 1 研究流程圖 20 圖3 - 2 後龍溪流域水系地理圖 23 圖3 - 3 後龍溪流域現有雨量站及流量站分布圖 25 圖3 - 4 徐昇氏多邊形法 32 圖3 - 5 等雨量線平均雨量法 32 圖3 - 6 後龍溪集水區雨量站徐昇氏多邊形圖 33 圖3 - 7 彼岸橋集水分區雨量站徐昇氏多邊形圖 34 圖3 - 8 打鹿坑集水分區雨量站徐昇氏多邊形圖 35 圖3 - 9 北勢大橋集水分區雨量站徐昇氏多邊形圖 36 圖3 - 10 彼岸橋集水分區土壤質地分布圖 43 圖3 - 11 打鹿坑集水分區土壤質地分布圖 44 圖3 - 12 北勢大橋集水分區土壤質地分布圖 45 圖3 - 13 彼岸橋集水分區土地利用分布圖 48 圖3 - 14 打鹿坑集水分區土地利用分布圖 49 圖3 - 15 北勢大橋集水分區土地利用分布圖 50 圖4 - 1 彼岸橋集水分區CN值分布圖 53 圖4 - 2 打鹿坑集水分區CN值分布圖 53 圖4 - 3 北勢大橋集水分區CN值分布圖 5