2022年獲得圖書館OA補助文章之介紹 (服務辦法)
  • 1. Agreement Between Caregivers’ Concerns of Children's Developmental Problems and Professional Identification in Taiwan.

    Lin, L.-Y., Yu, W.-H., Lin, W.-P., Chen, C.-C., & Tu, Y.-F. (2022). Frontiers in Pediatrics, 10 Read this article

    Early detection of developmental delays relies on the accuracy of the caregivers’ concerns of children’s developmental problems. The aim of this study was to investigate the agreement between the caregivers’ awareness of children’s developmental problems and professional identification. Caregivers of 1963 children (age range: 5–71 months; mean: 38.4 months) younger than 6 years old who were at risk of developmental delays and referred to the center for a comprehensive evaluation were enrolled in this study. The caregivers’ initial concerns of cognitive, speech/language, emotional/behavioral, motor and global development showed low agreement with the results of professional identification. The major disagreement was observed in the cognitive domain. Speech/language developmental concern was an important red-flag indicator of cognitive and emotional/behavioral developmental delays. The comorbid presence of ID, ASD, and ADHD was high in this study. Child’s age and mothers’ level of education were significant indicators for detecting the child’s developmental problems. It is recommended that assessing the cognitive developmental status is essential for all children in the identification process. Practitioners should not overlook caregivers' concern about speech/language and emotional/behavioral development. Transdisciplinary practitioners provide educational guidance to caregivers, especially in the domains of cognitive, speech/language, and emotional/behavioral development.

    早期發現兒童發展遲緩取決於照顧者對兒童發展問題關注的準確性。本研究的目的是調查照顧者對兒童發展問題的認識與專業評估結果之間的一致性。本研究招募了 1963 名 6 歲以下兒童(年齡範圍:5-71 個月;平均:38.4 個月)的照顧者,這些兒童因發展遲緩的風險被轉介到中心進行全面評估。照顧者對兒童的認知、語言、情緒/行為、動作和整體發展遲緩問題的關注與專業鑑定結果的一致性較低,尤其是認知領域的一致性最低。語言發展問題是認知和情緒/行為發展遲緩的重要危險信號。研究中發現有很高的比率同時伴隨智能障礙、自閉症和注意力不足過動症的共病。兒童的年齡和母親的教育程度是檢測孩子發展問題的重要指標。建議在鑑定過程中評估所有兒童的認知發展狀態是不可少的。臨床工作者不應忽視照顧者對語言和情緒/行為發展的關注。跨領域專業人員需要為照顧者提供衛教資訊,特別是在認知、語言和情緒/行為發展領域。

  • 2. Development and validation of a web-based prediction tool on minor physical anomalies for schizophrenia.

    Wang, X.-Y., Lin, J.-J., Lu, M.-K., Jang, F.-L., Tseng, H.-H., Chen, P.-S., Chen, P.-F., Chang, W.-H., Huang, C.-C., Lu, K.-M., Tan, H.-P., & Lin, S.-H. (2022). Schizophrenia, 8(1), 4. Read this article

    Minor physical anomalies (MPAs) have been suggested as biomarkers and potential pathophysiological significance for schizophrenia. However, an integrated, clinically useful tool that used qualitative and quantitative MPAs to visualize and predict schizophrenia risk while characterizing the degree of importance of MPA items was lacking. We recruited a training set and a validation set to conduct logistic regression and Lasso regression to select the best parameters of MPAs and constructed nomograms. Two nomograms were built to show the weights of these predictors. The results of the validation dataset verified the efficacy of the nomograms with the area under the curve 0.84 and 0.85 in the logistic regression model and lasso regression model, respectively. This study provides an easy-to-use tool based on validated risk models of schizophrenia and reflects a divergence in development between schizophrenia patients and healthy controls (https://www.szprediction.net/).

    在過往研究中細微體質特徵被認為是思覺失調症的生物標記,且有其潛在病理生理意義。然而,臨床缺乏用於測量思覺失調症風險的質性和量性細微體質特徵之整合工具。我們使用邏輯斯迴歸和Lasso迴歸來選擇最佳參數以nomogram視覺化方式來預測思覺失調症之風險。驗證數據集結果的兩種迴歸模型中曲線下面積分別為 0.84 和 0.85。本研究反應了思覺失調症患者與健康對照組的發展差異,並提供一種基於驗證思覺失調症風險模型的便利使用工具 (https://www.szprediction.net/)。

  • 3. Chemical Constituents of Hedyotis diffusa and Their Anti-Inflammatory Bioactivities.

    Hung, H.-Y., Cheng, K.-C., Kuo, P.-C., Chen, I.-T., Li, Y.-C., Hwang, T.-L., Lam, S.-H., & Wu, T.-S. (2022). Antioxidants, 11(2), 335. Read this article

    Seven new anthraquinones with rare 2-isopropyldihydrofuran (1–3) and 2,2-dimethylpyrano (4–7) moieties together with thirty-four known compounds were isolated from the extracts of whole Hedyotis diffusa plants. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among these isolates, selected compounds were examined for their anti-inflammatory activity. The results showed that rare substituted anthraquinones displayed potent inhibitory activity with IC50 values ranging from 0.15 ± 0.01 to 5.52 ± 1.59 µM on the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release cellular models. Meanwhile, the proposed drug target of the active anthraquinone was studied by computer modeling. The binding affinity between the anti-inflammatory anthraquinone and elastase was evaluated by molecular docking. These results provided the scientific insight into the medicinal values of Hedyotis diffusa and vision of development as lead compounds. (Abstract, Antioxidants, 2022, 11(2), 335)

    白花蛇舌草為常用的清熱解毒中草藥,本研究自全株植物之乙醇提取物中分離到41個天然化合物,其中新化合物1-3具有少見的2-isopropyldihydrofuran蒽醌骨架,而新化合物4-7具有2,2-dimethylpyrano蒽醌骨架,經由各種化學光譜和光譜分析方法對其結構進行了詳細的闡明和建立。在這些化合物中,篩選部分化合物進行抗發炎活性檢測,蒽醌類化合物對fMLP/CB誘導的超氧陰離子生成和彈性蛋白酶釋放具有很好的抑制活性,IC50 範圍在0.15 ± 0.01 ~ 5.52 ± 1.59 µM。同時,通過電腦模擬軟體,分子對接的方法研究抗發炎蒽醌與彈性蛋白酶的結合親和力推測。本研究結果為白花蛇舌草的藥用價值和蒽醌先導化合物的開發提供了部分科學依據。

  • 4. Incidence of Voice Disorders among Private School Teachers in Taiwan: A Nationwide Longitudinal Study.

    Chen, B.-L., Cheng, Y.-Y., Lin, C.-Y., & Guo, H.-R. (2022). International Journal of Environmental Research and Public Health, 19(3), 1130. Read this article

    Teachers are more likely to use a loud voice at work than the general working population, but few longitudinal studies have been conducted on their risk of voice disorders. The occurrence of voice disorders in private school teachers was assessed by using the Longitudinal Health Insurance Database 2000 of Taiwan. This study included private school teachers who were under 35 years old and newly employed between 2000 and 2010, and used workers with other occupations as the comparison cohort. After adjusting for age, sex, income, and comorbidities of sinusitis and laryngitis, private school teachers had a higher risk of developing voice disorders (hazard ratio [HR] = 1.58; 95% confidence intervals: 1.43–1.75). In addition, the finding that elementary and highschool teachers had a higher risk than college teachers (HR: 2.56 vs. 1.44) and the pattern of increases in cumulative incidence over time. The results support the causality between occupation and voice disorders in teachers.

    教師是聲帶疾患高風險族群,但較少縱貫性研究佐證。本研究利用台灣健保資料庫2000年版的百萬歸人檔,篩選出2000年至2010年間年齡少於35歲的新進私立學校教師,觀察他們的聲帶疾患發生情形,並與其他整體職業族群相對照。在校正年齡、性別、收入以及鼻竇炎、喉炎後,發現私校教師有較高罹患聲帶疾病風險(相對風險1.58,95%信賴區間1.43~1.75),且中小學較大專院校教師有更高風險(相對風險分別為2.56和1.44),暗示較長授課時數與管教需求的教師有更高的風險,進一步確立教師工作與聲帶疾患的因果關係。

  • 5. Association of retinopathy severity with cardiovascular and renal outcomes in patients with type 1 diabetes: a multi-state modeling analysis.

    Wang, W.-M., Ou, H.-T., Wen, M.-J., Su, P.-F., Yang, C.-Y., Kuo, T.-H., Wang, M.-C., & Lin, W.-H. (2022). Scientific Reports, 12(1), 4177. Read this article

    This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan’s National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.

    本研究目的在評估糖尿病視網膜病變 (DR) 嚴重程度對第一型糖尿病患者(T1D)患者主要不良心臟事件 (MACE) 和末期腎病變 (ESRD) 發生率的影響。研究對象為從台灣國民健康保險研究資料庫收錄1999年至2013年間被診斷患有T1D的病人,總共納入1135例患者,通過傾向評分匹配分為輕度DR(n = 454)、重度DR(n = 227)或無DR的對照組(n = 454)。進行了多狀態模型分析,本分析方式為競爭風險模型的擴展,並調整了特定過渡的協同變項,以預測隨後的MACE和ESRD。嚴重DR患者的MACE和ESRD風險顯著升高;與輕度DR和無DR患者相比,嚴重DR患者的MACE風險分別增加 2.97倍(1.73、5.07)和12.29倍(6.50、23.23);並且嚴重DR患者的ESRD風險分別比輕度DR組和無DR組高5.91倍(3.50, 9.99)和82.31倍(29.07, 233.04)(p < 0.001)。DR的嚴重程度與T1D患者的晚期糖尿病相關血管事件(即MACE和ESRD)顯著相關。

  • 6. Ge/Si multilayer epitaxy and removal of dislocations from Ge-nanosheet-channel MOSFETs.

    Chu, C.-L., Chang, J.-Y., Chen, P.-Y., Wang, P.-Y., Hsu, S.-H., & Chou, D. (2022). Scientific Reports, 12(1), 959. Read this article

    Horizontally stacked pure-Ge-nanosheet gate-all-around field-effect transistors were developed in this study. Large lattice mismatch Ge/Si multilayers were intentionally grown as the starting material rather than Ge/GeSi multilayers to acquire the benefits of the considerable difference in material properties of Ge and Si for realising selective etching. Additionally, dislocations were observed in suspended Ge nanosheets because of the absence of a Ge/Si interface and the disappearance of the dislocation-line tension force owing to the elongation of misfit dislocation at the interface. Forming gas annealing of the suspended Ge nanosheets resulted in a significant increase in the glide force compared to the dislocation-line tension force; the dislocations were easily removed because of this condition and the small size of the nanosheets. Based on this structure, a new mechanism of dislocation removal from suspended Ge nanosheet structures by annealing was described, which resulted in the structures exhibiting excellent gate control and electrical properties.

    本研究目標乃開發一個水平堆疊的純鍺納米片柵環場效應晶體管。以大晶格錯位的Ge/Si多層作為起始材料,而非多層之Ge/GeSi。透過利用Ge和Si的材料性質有很大差異的好處,以實現選擇性蝕刻之目的。此外,由於沒有 Ge/Si 界面,並且於界面處錯位的拉申,使位錯線張力消失。與位錯線張力相比,懸浮鍺納米片的形成氣體退火導致滑動力顯著增加;由於這種條件和納米片的小尺寸,位錯很容易去除。基於這種結構,描述了一種通過退火從懸浮的鍺納米片結構中去除錯位的新機制,從而使結構表現出優異的柵極控制和電學性能。

  • 7. Effects of symmetry breaking of the structurally-disordered Hamiltonian ensembles on the anisotropic decoherence of qubits.

    Chen, H.-B. (2022). Scientific Reports, 12(1), 2869. Read this article

    Hamiltonian ensemble (HE) is a novel approach to investigate the incoherent dynamical processes of quantum systems. It is particularly versatile in locally detecting bipartite quantum correlations and the characterization of the process nonclassicality. The HE theory is, in principle, applicable to very general unital dynamics; however, due to the technical difficulty imposed by the non-abelian algebraic structure underlying the HE, the results are exemplified under the frameworks of pure dephasing or isotropic depolarization. In this work, I achieve to circumvent the algebraic difficulty and go further beyond the aforementioned two frameworks, reaching the regime of anisotropic decoherence. A new type of HE of structural disorder in canonical form is studied. The disorder is categorized according to different levels of symmetry of its geometry. I have demonstrated four levels of symmetry, from the most symmetric case of spherical symmetry to the discrete type of simultaneous reflectional symmetries. This enables us to clearly distinguish how the different incoherent dynamical behaviors are caused by various types of symmetry breaking. These results significantly enhance the applicability the HE-simulation of open quantum systems.

    哈密頓量系綜集合表示法是近年來新發展起來的工具,可用來研究量子系統的消相干動力學過程。當應用這個方法在局部地偵測量子關聯性、描述與量化消相干動力學過程中展現出的非古典性時又特別的有用。儘管本方法理論上可以廣泛應用在各類型的消相干動力學過程中,然而,由於本方法其內在的非阿貝爾代數結構之故,使得其廣泛應用性會遇到許多數學上的困難,致使目前大多數的工作僅用其來描述特定簡化類型的動力學過程,如純消相位過程或各向均勻去極化過程。在本工作中,我們成功克服一些數學代數結構方面的困難,突破以往的研究限制框架,達到各向非均勻去極化過程。因此這裡可以研究一種新類型的哈密頓量系綜集合,我們稱之為結構性的無序。這類結構性的無序可根據其無序分布的對稱性而加以有條理的分類與研究,讓我們可以了解不同的消相干行為是由甚麼類型的對稱性破缺引起。這些研究成果使的哈密頓量系綜集合理論的應用性可以更加廣泛。

  • 8. Hyperuricemia Is Associated with Significant Liver Fibrosis in Subjects with Nonalcoholic Fatty Liver Disease, but Not in Subjects without It.

    Yen, P.-C., Chou, Y.-T., Li, C.-H., Sun, Z.-J., Wu, C.-H., Chang, Y.-F., Lu, F.-H., Yang, Y.-C., Chang, C.-J., & Wu, J.-S. (2022). Journal of Clinical Medicine, 11(5), 1445. Read this article

    Liver fibrosis is associated with liver-related outcomes, yet often underdiagnosed in the primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We investigated the association between hyperuricemia and liver fibrosis in subjects with and without NAFLD. This study recruited 11,690 relevant participants from a health-checkup center. Hyperuricemia was positively associated with significant liver fibrosis (p = 0.001) in the logistic regression. The positive association of hyperuricemia with significant liver fibrosis remained in subjects with NAFLD (p = 0.001), but not in subjects without NAFLD.

    肝纖維化與肝相關的結果相關,但在基層醫療卻時常被忽略。高尿酸血症與非酒精性脂肪肝(NAFLD)有關,但與肝纖維化的關係仍未明。過去研究資料在沒有NAFLD的族群者資料有限。本篇研究探討在有無NAFLD的病人,其高尿酸血症及肝纖維化的相關性。此篇收錄11690位至健康檢查中心、符合收錄條件的成年人。經過邏輯式迴歸,高尿酸血症與顯著肝纖維化成正相關(p = 0.001),且其正相關僅見於有NAFLD的族群,而不見於無NAFLD的族群。

  • 9. VLSI Architecture of S-Box With High Area Efficiency Based on Composite Field Arithmetic.

    Teng, Y. T., Chin, W. L., Chang, D. K., Chen, P. Y., & Chen, P. W. (2022). IEEE Access 10,2721-2728. Read this article

    This work aims at optimizing the hardware implementation of the SubBytes and inverse SubBytes operations in the advanced encryption standard (AES). To this, the composite field arithmetic (CFA) is employed to optimize all building blocks in S-box (and inverse S-box) of SubBytes (and inverse SubBytes) transformation. A joint design of S-box and inverse S-box is also proposed to further enhance the area efficiency. Specifically, the area of multiplier in the Galois composite field, GF((22)2), is reduced. The squaring and multiplication with constant λ in GF((22)2) are combined and optimized as well. Moreover, the multiplicative inversion in GF((22)2) is manually optimized. Furthermore, the S-box and inverse S-box are combined and optimized using the pre_processing and post_processing modules. To increase the throughput, a balanced and pipelined architecture is derived. Using the proposed architecture, a throughput of 5.79 Gbps for the S-box can be achieved on Virtex-6 XC6VLX240T and 10% better than the conventional work. According to the ASIC implementation result, the proposed design can still achieve the highest area efficiency and approximately 30% better than conventional works using TSMC 90nm process.

    這項工作旨在優化高級加密標準 (AES) 中SubBytes和反SubBytes操作的硬件實現。為此,採用複合域算法(CFA)優化SubBytes(和逆SubBytes)變換的S盒(和逆S盒)中的所有構建塊。還提出了S盒和逆S盒的聯合設計,以進一步提高面積效率。具體來說,伽羅瓦複合域中乘數的面積GF((22)2)減少了。 GF((22)2)中常數λ的平方和乘法也被組合和優化。此外,GF((22)2)中的乘法反元素是手動優化的。此外,使用 pre_processing 和 post_processing 模塊對S盒和逆S盒進行組合和優化。為了增加吞吐量,衍生出一種平衡的流水線架構。使用所提出的架構,S盒的吞吐量可以在 Virtex-6 XC6VLX240T 上實現 5.79 Gbps,比傳統工作高 10%。根據 ASIC 的實現結果,所提出的設計仍然可以達到最高的面積效率,並且比使用台積電 90nm 工藝的傳統作品好約 30%。

  • 10. Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy.

    Chen, Y.-C., Lu, B.-Z., Shu, Y.-C., & Sun, Y.-T. (2022). Frontiers in Endocrinology, 12.2721-2728. Read this article

    Aims: Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM). Methods: Ktrans was crossectional measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).Results: In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was prior to the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds was most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions: This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, prior to the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

  • 11. Solving Inverse Electrocardiographic Mapping Using Machine Learning and Deep Learning Frameworks.

    Chen, K.-W., Bear, L., & Lin, C.-W. (2022). Sensors, 22(6),2331. Read this article

    Electrocardiographic imaging (ECGi) reconstructs electrograms at the heart’s surface using the potentials recorded at the body’s surface. This is called the inverse problem of electrocardiography. This study aimed to improve on the current solution methods using machine learning and deep learning frameworks. Electrocardiograms were simultaneously recorded from pigs’ ventricles and their body surfaces. The Fully Connected Neural network (FCN), Long Short-term Memory (LSTM), Convolutional Neural Network (CNN) methods were used for constructing the model. A method is developed to align the data across different pigs. We evaluated the method using leave-one-out cross-validation. For the best result, the overall median of the correlation coefficient of the predicted ECG wave was 0.74. This study demonstrated that a neural network can be used to solve the inverse problem of ECGi with relatively small datasets, with an accuracy compatible with current standard methods.

    心臟電位影像重建(Electrocardiographic imaging)是基於體表所測得之心電圖,重建心臟表面或內部的電位分佈的過程。此問題亦被稱為反向問題(Inverse Problem)。由於此問題在本質上無法得出唯一解,以及不容易針對體表與心臟間的電傳導性建模,目前針對此問題所發展出的方法,其準確度約0.7(所重建的心電圖與實際心電圖之間相關系數之中位數)。本研究嘗試使用神經網路解決此問題,以增加模型的準確度。本研究使用之兩組資料,一是來自於豬體表所量測之多個心電圖訊號,二是同時量測之豬心臟表面的心電圖。第一部分的研究,訓練與測試模型的資料皆來自同一之豬。所使用之神經網路有兩種。一是由數個全連接層(Fully Connected Layer FCN)所組成之神經網路,二是由長短期記憶(Long Short-Term Memory LSTM)神經網路所組成。第二部分的研究,我們將來源於不同的五隻豬之資料進行轉換,加以統合。接著我們使用卷積神經網絡(Convolutional Neural Network CNN)來建立模型。本研究使用留一驗證(leave-one-out cross-validation)作為模型準確度的驗證方法。若比較重建的心臟表面心電圖與實際心電圖,在第一部分研究中,使用全連接層FCN之部分,整體的相關系數之中位數以及前四分之一與後四分之一的數值為0.90 [0.68–0.96]。使用全連接層LSTM之部分則為0.82 [0.54–0.93]。在第二部分研究,使用CNN,整體的相關系數之中位數以及前四分之一與後四分之一的數值則為0.74 [0.22–0.89]。若比較重建的激發時間圖(activation map),在第一部分研究中,使用全連接層FCN之部分,整體的相關系數之中位數以及前四分之一與後四分之一的數值為0.86 [0.61–0.93]。使用全連接層LSTM之部分則為0.52 [0.05–0.80]。在第二部分研究,使用CNN,整體的相關系數之中位數以及前四分之一與後四分之一的數值則為0.82 [0.67–0.93]。若比較激發點位置誤差(localization error),在第一部分研究中,使用全連接層FCN之部分,整體的距離之中位數以及前四分之一與後四分之一的數值為10.4 [3.6–22.6] mm。使用全連接層LSTM之部分則為18.5 [6.4–41.5] mm。在第二部分研究,使用CNN,整體的相關系數之中位數以及前四分之一與後四分之一的數值則為9.3 [3.4–17.0] mm。本研究顯示,針對心臟電位影像重建,我們可以使用相對少量的資料解決。我們所達到的最佳結果為0.74(所重建的心電圖與實際心電圖之間相關系數之中位數)。此外,本研究也顯示並不需要精確的座標資訊來重建心電圖。針對模型的準確性而言,在不同的豬隻與不同的量測結果之歧異度仍然很大。這可能與資料量相對較小有關,這可以在第二部分研究中看到。其整體準確度較佳,可能與其整合了所有的資料,其資料量較第一部分多有關。臨床應用部分,此研究顯示可使用非侵入性的體表量測心電圖,來找尋心臟的電刺激源點。此資訊可用於心室早期收縮病人之治療。

  • 12. Highly Efficient Adsorption of Sr2+ and Co2+ Ions by Ambient Prepared Alkali Activated Metakaolin.

    Huang, Y.-H., & Wu, Y.-C. (2022). Polymers, 14(5),992. Read this article

    This study aimed to explore a low cost and sustainable adsorbent to remove Sr2+ and Co2+ ions, which are major radioactive ions in nuclear wastewater. The material properties of the alkali-activated metakaoline as a function of soaking time at ambient temperature from 1 day to 7 days were examined by XRD, XRF, SEM, and solid-state NMR. Adsorption isotherms were used to evaluate the appropriate soaking time for optimal sorption performance for both Sr2+ and Co2+ ions. The alkali-activated metakaolin soaked for 3 days (BK3) presented the maximum adsorption capacities of 3.81 meq/g (167.5 mg/g) and 4.02 meq/g (118.5 mg/g) for Sr2+ and Co2+, respectively. The sorption mechanisms for Sr2+ and Co2+ in the BK3 sample were investigated, and the experimental results indicated that adsorption for Sr2+ was achieved via ion exchange. By contrast, surface complexation in combination with ion exchange contributed to the sorption mechanisms for the removal of Co2+. Competitive adsorption experiments revealed that the alkali-activated metakaolin favored the adsorption for divalent ions (i.e., Sr22+ and Co2+), and it was less effective for Cs+. Finally, the used adsorbent could be directly mineralized and vitrified by heat treatment to immobilize the Sr2+ and Co2+ ions.

    本研究旨在開發具有量產潛力且符合永續發展的無機吸附劑,用於去除核廢水的Sr2+與Co2+放射性離子。使用天然高嶺土作為原料,在常溫下以氫氧化鈉進行鹼活化處理,觀察並討論不同鹼活化時間(1至7天),對於高嶺土的結構變化情形。批次等溫吸附實驗確認,常溫鹼活化3天之樣品(BK3)對Sr2+與Co2+離子具有最高之吸附效率,分別為 3.81 meq/g (167.5 mg/g) 與4.02 meq/g (118.5 mg/g) 。研究結果亦指出,BK3樣品對Sr2+離子的吸附是由離子交換機制所主導,而對Co2+則是由表面錯合反應結合離子交換兩種機制綜合發生。競爭性離子吸附實驗發現,BK3樣品對於二價離子(Sr2+與Co2+)具有較高的選擇性吸附能力。本研究所合成之吸附劑以容易取得且價格低廉之天然礦物為原料,在常溫下即可獲得高效率之無機離子吸附劑,而完成離子吸附工作後之吸附劑廢料,可藉由熱處理將離子直接礦化於結構中,達到離子封存的目的,在核廢料處理的應用上具有高度潛力。

  • 13. The association between osteoporosis medications and lowered all-cause mortality after hip or vertebral fracture in older and oldest-old adults: a nationwide population-based study.

    Li, C.-C., Hsu, J. C., Liang, F.-W., Chang, Y.-F., Chiu, C.-J., & Wu, C.-H. (2022). Aging, 14(5),2239-2251. Read this article

    Osteoporotic fracture is a common public-health problem in ageing societies. Although post-fracture usage of osteoporosis medications may reduce mortality, recent results have been inconsistent. Participants aged 65 years old and older newly diagnosed with both osteoporosis and hip or vertebral fractures within 2009-2017 were recruited from Taiwan National Health Insurance Research Database. Osteoporosis medication exposure was calculated after the first-time ambulatory visit with newly diagnosed osteoporosis. Patients were followed until death or censored at the end of 2018. A total of 87,935 participants aged 65 years old and over (73.4% female), with a mean 4.13 follow-up years, were included. Taking medication was associated with significantly lower risk of mortality, even in the oldest-old adults, where a longer duration of taking osteoporosis medication was associated with lower all-cause mortality. Specific causes of mortality were also significantly lower for participants taking osteoporosis medication, such as cancer and cardiovascular disease. In conclusion, osteoporosis medication after hip or vertebral fracture may reduce mortality risk in older adults, notably in oldest-old adults. Encouraging the use of post-fracture osteoporosis medication in healthcare policies is warranted.

    骨鬆性骨折是高齡化社會中常見的公共衛生問題。儘管骨折後使用骨質疏鬆症藥物可能會降低死亡率,但最近的研究結果並不一致。本研究從台灣全民健保資料庫中篩選2009~2017年間新診斷骨質疏鬆症且髖部或脊椎骨折的65歲及以上參與者,並追蹤至2018年。骨鬆藥物暴露是從第一次門診開立骨鬆藥物後開始計算。共計87,935名65歲及以上的參與者(73.4%為女性)進入本研究,平均追蹤時間為4.13年。研究結果顯示,使用骨鬆藥物可顯著降低骨鬆骨折後的全死因死亡率,即使是85歲以上的老人。使用骨鬆藥物的時間越長,死亡風險越小。而使用骨鬆藥物亦可顯著降低骨鬆骨折後的常見死因死亡率,如癌症和心血管疾病。因此,鼓勵在醫療政策中,在骨鬆骨折後使用骨鬆藥物是必要的。

  • 14. Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.

    Hsieh, Y.-P., Chen, K.-C., Chen, M.-Y., Huang, L.-Y., Su, A.-Y., Chiang, W.-F., Huang, W.-T., & Huang, T.-T. (2022). International Journal of Molecular Sciences , 23(9), 4495. Read this article

    Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underly- ing carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

    蛋白質酪氨酸激酶6表觀基因體調控失調促進口腔鱗狀細胞癌的癌變
    口腔鱗狀細胞癌佔所有口腔癌類型的90%以上,並且會導致相當高的死亡率。表觀基因體調控異常是常見的致癌機制。DN甲基化調控異常會使正常細胞轉化為癌前病變細胞最終轉變成癌細胞。在本研究中,調查了口腔鱗狀細胞癌發展過程中PTK6的DNA甲基化調控。在此研究中,透過亞硫酸氫鹽基因組DNA測序來確定PTK6甲基化水平。以及建立口腔鱗狀細胞癌動物模型來檢查,在口腔鱗狀細胞癌不同階段中PTK6的表達差異。在口腔鱗狀細胞癌的發展過程中,PTK6 的DNA甲基化顯著降低。與人類正常口腔角質細胞相比,口腔鱗狀細胞癌細胞株中PTK6的mRNA和蛋白質表達顯著增加。在動物模型中,利用4-硝基喹啉1-氧化物和檳榔鹼處理後,PTK6的甲基化水平顯著降低,而PTK6的mRNA和蛋白表達顯著增加。從這些結果可以發現,PTK6低甲基化可以作為口腔鱗狀細胞癌的診斷標誌物。在口腔鱗狀細胞癌中, PTK6的表現增加促進了口腔鱗狀細胞癌細胞的增殖、遷移和侵襲。 PTK6通過增加STAT3磷酸化和ZEB1表達促進癌變和轉移。 PTK6的表觀遺傳失調可作為早期檢測OSCC的生物標誌物和治療標的。

  • 15. Development of a Self-Viscosity and Temperature-Compensated Technique for Highly Stable and Highly Sensitive Bead-Based Diffusometry.

    Chen, W.-L., & Chuang, H.-S. (2022). Biosensors , 12(6), 362. Read this article

    Brownian motion, which is a natural phenomenon, has attracted numerous researchers and received extensive studies over the past decades. The effort contributes to the discovery of optical diffusometry, which is commonly used for micro/nano particle sizing. However, the analysis uncertainty caused by the coupling relationship among particle diameter, temperature, and fluid viscosity usually poses a barrier to precise measurement. Preventing random background noise becomes the key to achieving a high level of accuracy in diffusometry detection. Recently, Janus particles have become known as an ideal tool for resolving the rotational Brownian motion. Followed by our previous study, the rotational Brownian motion and the translational Brownian motion can be separately measured using the Janus particles. Accordingly, a simple self-viscosity and temperature-compensated technique based on the delicate removal of temperature and fluid viscosity variations through particle tracking was first proposed in this study. Consequently, the translational Brownian motion was expressed in terms of particle trajectory, whereas the rotational Brownian motion was expressed in terms of the blinking signal from the Janus particles. The algorithm was verified simulatively and experimentally in temperature (10 °C to 40 °C) and viscosity-controlled (1 mPa·s to 5 mPa·s) fields. In an evaluation of biosensing for a target protein, IFN-γ, the limit of detection of the proposed self-compensated diffusometry reached 0.45 pg/mL, whereas its uncertainties of viscosity and temperature were 96 and 15-fold lower than the pure the rotational Brownian motion counterpart, respectively. The results indicated the low-uncertainty and high-accuracy biosensing capability resulting from the self-viscosity and temperature-compensated technique. This research will provide a potential alternative to future similar bead-based immunosensing, which requires ultra-high stability and sensitivity.

    布朗運動是一種自然現象,在過去的數十年裡,吸引了相當多的科研人員投入研究,而這一連串的努力最終也促成了光學擴散儀的發展。光學擴散儀通常用於奈/微米粒子粒徑的測定;然而,由於粒徑、液體溫度和粘度之間具有相互耦合關系,因此易引起分析不確定性,對精確測量構成阻礙。為此,降低背景雜訊便成為擴散測量法實現高精確度的首要關鍵。近來,雙性粒子已成為量化旋轉布朗運動的一項理想工具。根據我們之前的研究,旋轉布朗運動和位移布朗運動皆可以透過雙性粒子分別測定。因此,本研究提出了一種簡單的自我黏度和溫度補償技術,希望透過追蹤粒子巧妙去除流體溫度和黏度變化的影響。原則上,位移布朗運動可由粒子軌跡來顯示,而旋轉布朗運動則用雙性粒子的閃爍信號來表示。該演算法已在控制溫度(10 °C至40 °C)和黏度(1 mPa·s至5 mPa·s)範圍內成功地進行了模擬和實驗驗證。最後,我們還利用一種指標蛋白,IFN-γ,來評估本技術在生物感測方面的效果。結果顯示檢測極限可達到0.45 pg/mL,而黏度和溫度的不確定性分別比單純利用旋轉布朗運動的方法低了將近96倍和15倍。這些結果顯示,本研究中的自我黏度和溫度補償技術具有低不確定性和高精度的生物感測能力。這項研究預期可為未來需要超高穩定性和靈敏度之類似微珠免疫感測應用提供一個潛在的替代方案。

  • 16. Systematic Screening of Penetratin’s Protein Targets by Yeast Proteome Microarrays.

    Shah, P., & Chen, C.-S. (2022). International Journal of Molecular Sciences , 23(2), 712. Read this article

    Cell-penetrating peptides (CPPs) have distinct properties to translocate across cell envelope. The key property of CPPs to translocation with attached molecules has been utilized as vehicles for the delivery of several potential drug candidates that illustrate the significant effect in in-vitro experiment but fail in in-vivo experiment due to selectively permeable nature of cell envelop. Penetratin, a well-known CPP identified from the third α-helix of Antennapedia homeodomain of Drosophila, has been widely used and studied for the delivery of bioactive molecules to treat cancers, stroke, and infections caused by pathogenic organisms. Few studies have demonstrated that penetratin directly possesses antimicrobial activities against bacterial and fungal pathogens; however, the mechanism is unknown. In this study, we have utilized the power of high-throughput Saccharomyces cerevisiae proteome microarrays to screen all the potential protein targets of penetratin. Saccharomyces cerevisiae proteome microarrays assays of penetratin followed by statistical analysis depicted 123 Saccharomyces cerevisiae proteins as the protein targets of penetratin out of ~5800 Saccharomyces cerevisiae proteins. To understand the target patterns of penetratin, enrichment analyses were conducted using 123 protein targets. In biological process: ribonucleoprotein complex biogenesis, nucleic acid metabolic process, actin filament-based process, transcription, DNA-templated, and negative regulation of gene expression are a few significantly enriched terms. Cytoplasm, nucleus, and cell-organelles are enriched terms for cellular component. Protein-protein interactions network depicted ribonucleoprotein complex biogenesis, cortical cytoskeleton, and histone binding, which represent the major enriched terms for the 123 protein targets of penetratin. We also compared the protein targets of penetratin and intracellular protein targets of antifungal AMPs (Lfcin B, Histatin-5, and Sub-5). The comparison results showed few unique proteins between penetratin and AMPs. Nucleic acid metabolic process and cellular component disassembly were the common enrichment terms for penetratin and three AMPs. Penetratin shows unique enrichment items that are related to DNA biological process. Moreover, motif enrichment analysis depicted different enriched motifs in the protein targets of penetratin, LfcinB, Histatin-5, and Sub-5.

    細胞穿透胜肽(CPP)有跨越細胞膜的明顯特性,CPP和附著分子有跨細胞膜的關鍵特性被用來運送許多具有潛力的藥物,在體外試驗有顯著效果,但在體內試驗失敗是因為有細胞膜的選擇性通透關係。Penetratin是一種著名的CPP源自於觸角族同域的黑腹果蠅的第三阿法-螺旋,被廣泛利用或研究在傳遞生物活性分子以治療癌症、中風、和由致病微生物所引起的感染。少許研究有說明penetratin擁有對抗細菌與真菌病原體的活性;然而這個機轉是未知的。在此研究中,我們使用高通量釀酒酵母菌蛋白質微陣列的技術來分析在penetratin潛在所攻擊的目標蛋白。運用釀酒酵母菌微陣列分析penetratin,並進行統計分析,其中約5800個釀酒酵母的蛋白質中有123個是penetratin的目標蛋白。為了瞭解penertratin的目標蛋白特性,此123種目標蛋白被進行富集分析。在生物程序方面:核蛋白複合物生物產生、核酸代謝過程、肌動蛋白纖維-基本過程、轉譯、DNA-模板、基因表現的負控制都是一些顯著富集的特性。細胞質、細胞核、胞器都是這些蛋白質富集的細胞部位。蛋白質和蛋白質相互作用分析描述這123 蛋白質的特性在於核蛋白複合物的生物產生、皮質細胞骨架和組蛋白結合方式,他們代表123種penetratin目標蛋白的主要富集的特性。我們也比較penetratin目標蛋白和其他抗真菌AMPs(Lfcin B, Histatin-5, and sub-5)細胞內的目標蛋白。比較結果顯示penetratin和AMPs間有少許獨特的蛋白質。核酸代謝和細胞成份分解是pentratin和三種AMPs 共同的富集特性。Penetratin 獨特富集的項目和DNA生物過程有關。此外,基序豐富度分析結果得知penetratin ,Lfcin B,Histatin-5,and Sub-5目標蛋白中,有不同富集的基序。

  • 17. Effects of percutaneous vertebroplasty on respiratory parameters in patients with osteoporotic vertebral compression fractures.

    Ma, C.-H., Yang, H.-L., Huang, Y.-T., Wu, Z.-X., Cheng, H.-C., Chou, W.-C., Hung, C.-H., & Tsai, K.-L. (2022). Annals of Medicine , 54(1), 1320-1327. Read this article

    Vertebral compression fractures (VCFs) often occur in patients with osteoporosis. These fractures can also lead to postural changes. Several studies have shown that patients with vertebral compression fractures have a restrictive pattern in their pulmonary function. Percutaneous vertebroplasty (PVP) is the standard treatment for vertebral compression fractures, with the benefits of pain relief and enhancement of vertebral stability for partially collapsed vertebral bodies. However, the effects of PVP on short-term recovery of respiratory performance have not been investigated. Therefore, this study aimed to examine the changes in pulmonary function, respiratory muscle strength, maximal voluntary ventilation (MVV), and chest mobility in patients with vertebral compression fractures after PVP. We recruited 32 VCF patients. Four time points were measured: before and after PVP and 1 and 3 weeks after PVP. Chest expansion and back pain improved at each time point after PVP. MVV showed significant progress at both 1 and 3 weeks after discharge. Forced expiratory volume in 1 second (FEV1) and maximal inspiratory muscle strength significantly improved one week after discharge. Taking all the data together, PVP can resolve severe back pain and provide excellent improvements in MVV and chest mobility in patients with vertebral compression fractures.

    脊椎椎體壓迫性骨折經常發生在骨質疏鬆症患者身上。這些骨折可能導致姿勢變化。多項研究指出,脊椎椎體壓迫性骨折患者的肺功能存在限制性模式。經皮椎體成形術是脊椎椎體壓迫性骨折的標準治療方法,具有緩解疼痛和增強部分塌陷椎體的椎體穩定性的好處。然而,尚未研究驗證對經皮椎體成形術呼吸性能短期恢復的影響。因此,本研究旨在驗證經皮椎體成形術後對脊椎椎體壓迫性骨折患者肺功能、呼吸肌力量、最大自主通氣量和胸部活動度的變化。我們招募了 32 名脊椎椎體壓迫性骨折患者。測量了四個時間點:經皮椎體成形術前和之後以及經皮椎體成形術後1和3週。經皮椎體成形術後每個時間點的胸脹和背痛都有所改善。 最大自主通氣量在出院後 1 周和 3 週均顯示出顯著進展。出院一周後,1秒用力呼氣量最大吸氣肌力顯著改善。綜合所有數據,經皮椎體成形術不僅可以解決嚴重的背痛,還可以顯著改善脊椎椎體壓迫性骨折患者的最大自主通氣量和胸部活動度。

  • 18. Highly Transparent and Polarization-Maintained Terahertz Plasmonic Metamaterials Based on Metal-Wire-Woven Hole Arrays: Fundamentals and Characterization of Transmission Spectral Peaks.

    You, B., Lu, J.-Y., Chen, P.-L., Hung, T.-Y., & Yu, C.-P. (2022). Materials , 15(5), 1871. Read this article

    Metal-hole-supported terahertz (THz) waves through the structure of a metal-wire-woven hole array (MWW-HA) present high-frequency-passed transmittance spectra of one plasmonic metamaterial with artificial plasmonic frequencies, which are inversely proportional to metal-hole widths. For the transmitted THz waves of MWW-HA, transverse-electric (TE) and transverse-magnetic (TM) waveguide modes mix within a symmetric metal-hole boundary. THz resonance waves transversely crossing the holes of MWW-HA are experimentally characterized with spectral peaks in the frequency range of 0.1–2 THz that are correlated with aperture sizes, unit-cell-hole widths, metal-wire thicknesses, and wire-bending angles. The metal-hole-transported resonance waves of MWW-HA are dominated by TE waveguide modes instead of TM ones because a hole width of MWW-HA is approximate to the half wavelength of a resonance wave. The round metal edges of the woven metal wires can minimize the effective optical length of a thick metal hole to transmit THz resonance waves, thereby resulting the smallest rotation angle of linear polarization and high transmittance up to 0.94. An MWW-HA structure is therefore reliable for supporting metal-hole resonance waves with low resistance, whereas a metal-slab-perforated hole array cannot achieve the same result.

    此研究發表以金屬線編織網的孔洞結構所傳輸的兆赫電磁波,發現具有電漿人造結構的高頻通過頻譜特徵與類似金屬電漿頻率的截止頻率表現,此高通頻譜與其截止頻率反比於編織網孔洞尺寸,由於金屬孔洞的二維對稱性,編織網孔洞內的兆赫電磁波是由橫向電波與橫向磁波,所混合而成的波導電場模態,此混合電場是經由橫向共振模式通過金屬編織網,其頻譜所展現的穿透率尖峰現象,是因為此兆赫頻率符合電磁波在金屬孔洞內的共振尺寸條件,包括孔徑尺寸、單元體結構寬度、金屬線徑與金屬線曲折角度等,並且經由共振過程的縱向消逝波,將0.1–2 THz兆赫波能量傳遞到出射端面,此外,經由調查比較穿透頻譜頻率與金屬孔洞寬度,證實橫向電波控制整體金屬編織網的穿透頻譜特徵,另外,金屬線的圓形狀表面可以縮減兆赫共振波傳輸的光學厚度,造成最低幅度的極化偏離表現,此實驗研究觀察最高穿透率可以達到0.94左右,不同於平板式金屬孔洞陣列的兆赫波穿透特性,此研究成功證實金屬編織孔洞陣列,不但能夠共振傳輸兆赫電磁波,還可以表現低損耗、保持極化偏振的特殊表現。

  • 19. Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study.

    Chou, C.-Y., Cheng, W.-F., Chen, M.-Y., Lin, H., Ho, C.-M., Hung, Y.-C., Huang, L.-W., Wang, P.-H., Yu, M.-H., & Huang, Y.-F. (2022). Cancers , 14(7), 1746. Read this article

    This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemoresponse independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. Cancers 2022, A PFI of < 7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.

    卵巢癌死亡率在婦女癌症死因中名列前茅,其中卵巢亮細胞癌是一種特殊難治的亞型。此協作研究目的在提供台灣大規模亮細胞癌臨床個案特性及治療相關之長期預後因子,以及開發鉑敏感分級的新穎臨床標準。研究設計為以九家醫學中心回溯性收集1995年至2015年診斷為卵巢亮細胞癌病人之詳細臨床資訊及分析病人特性與治療相關之復發或死亡風險。最後共收集536位病人,中位追蹤期為36.6個月。資料分析也發現無惡化期間採用<7個月為鉑抗藥性、7-14個月為部分鉑抗藥性、及>14個月為鉑敏感性作為亮細胞癌之鉑敏感分級的新穎臨床標準,有別於常見之漿液型癌以6及12個月做為切點。多變數分析發現早期亮細胞癌的治療前CA125及對化學治療反應可做為無惡化存活期之獨立預測因子;首次疾病惡化後的減癌手術則可降低死亡率。亮細胞癌旁同時有子宮內膜異位存在、生育功能保留手術、或鉑藥物合併如paclitaxel或cyclophosphamide,則對早期癌病預後沒有明顯影響。我們發現,無惡化期間<7個月是預測疾病惡化或死亡風險上,同時也是預測第二次疾病惡化上的獨立風險因子。檢測無惡化期間<7個月的角色,的確也與化學治療抗藥性及晚期癌病明顯相關、並有較短的首次復發後之存活期。我們觀察到,尤其是晚期亮細胞癌病人,以鉑化合物併用他種化學治療藥物類別治療,無論是第一線時或是復發時使用,對於提升存活期的效果相當有限。因此未來應該在晚期、或第一次復發若在首次化療結束後<7個月內就被發現之卵巢亮細胞癌族群,就應該鼓勵進入臨床試驗,以探討新穎生物鉑抗藥性指標或採用特殊標靶治療的策略,或能提升這種具鉑抗藥性卵巢癌患者的存活。

  • 20. Discovery of 5,7-Dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one with Lipid Lowering Effects in Hepatocytes.

    Chang, Y.-H., Yen, C.-H., Lai, C.-C., Lai, H.-Y., & Hung, H.-Y. (2022). Pharmaceuticals , 15(4), 449. Read this article

    Although the population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing, there is still no medicine indicated for treating these diseases clinically. Therefore, a new drug to overcome NAFLD and NASH is in urgent need. Capillarisin, a 2-phenoxychromone isolated from Artemisia capillaris Thunb., is well-known for its liver-protective effects. Thus, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells. The results showed that modification of trimethoxy groups on the phenyl ring possessed better inhibitory properties compared to other functional groups on the same ring. Surprisingly, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one, with an IC50 value of 32.2 ± 2.1 μM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.

    雖然酒精性肝炎跟非酒精性肝炎的盛行率有增加的趨勢,但臨床上並沒有治療的藥物。因此,開發治療酒精性肝炎跟非酒精性肝炎的新藥有其急迫性。茵陳色原酮為分離自茵陳蒿植物且具有2-苯氧基色原酮結構的化合物,其保肝作用是已為人知曉的。因此,一系列具有2-苯氧基色原酮結構的衍生物就被製備出來並測試其在Huh-7肝癌細胞株上對於油酸誘導的脂肪累積的保護效果。結果顯示化學修飾在苯環上具有三個甲氧基的化合物比起其他的官能基修飾具有較高的抑制油滴累積的能力。令人驚訝的是在五號位置上有羥基的結構表現出明顯的細胞毒性。最後,最有效的化合物表現出抑制脂肪累積的百分之五十的濃度32.3 μM且沒有明顯的細胞毒性,此作用透過轉錄輔助活化因子(PGC1α)來促進脂肪的代謝。這個研究結果對於未來繼續開發治療酒精性肝炎跟非酒精性肝炎非常的有幫助。

  • 21. Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats.

    Lin, M.-W., Fang, S.-Y., Hsu, J.-Y. C., Huang, C.-Y., Lee, P.-H., Huang, C.-C., Chen, H.-F., Lam, C.-F., & Lee, J.-S. (2022). Frontiers in Neuroscience , 16. Read this article

    Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-μg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI.

    嚴重脊髓損傷後會造成永久性的神經功能障礙,在臨床上至今仍沒有有效的治療方法,不僅影響患者個人身體和心理,對負擔照顧責任的家屬與社會帶來相當大的負荷;因為細胞在死亡前都會發生粒線體功能障礙,如何提升粒線體功能一直是研究的重要方向,本篇論文驗證移植健康的粒線體在外傷性脊髓損傷的治療成效,因為粒線體可用自體採集,沒有免疫排斥性,可以很快進入臨床試驗,我們希望對脊髓損傷提出一個全新的治療方式,為脊髓損傷病人提供一個希望。

  • 22. Investigating the clinical implication of corneometer and mexameter readings towards objective, efficient evaluation of psoriasis vulgaris severity.

    Hsu, C.-K., Cheng, N.-Y., Yang, C.-C., Yen, Y.-Y., & Tseng, S.-H. (2022). Scientific Reports , 12(1), 7469. Read this article

    Currently, there are already commercial systems, such as the Courage+Khazaka Corneometer and Mexameter that measure skin capacitance and optical reflectance, for conveniently quantifying the status of skin barrier function and erythema of skin. Despite numerous comparisons of the Courage+Khazaka system with the PASI scoring system, they are rarely compared on parity with diffuse reflectance spectroscopy (DRS) based systems. In this study, we employed a custom-built DRS system shown to be able to determine the skin water-protein binding status and the hemoglobin concentration, and we performed cross-validation of the DRS measurement results with the readings derived from the Corneometer and Mexameter as well as a portion of the PASI scores. We conclude that the DRS method could be a valuable addition to existing skin capacitance/reflectance measurement systems and the PASI scoring system toward achieving a more efficient and objective clinical psoriasis vulgaris severity evaluation.

    目前,已經有商業系統,例如 Courage+Khazaka Corneometer 和 Mexameter 測量皮膚電容和光學反射率,可以方便地量化皮膚屏障功能和皮膚紅斑的狀態。有不少過往文獻針對Courage+Khazaka 系統與 PASI 評分系統進行比較,但很少有文獻將上述系統與漫反射光譜 (DRS) 系統進行比較。在這項研究中,我們使用了一個自製的 DRS 系統,該系統能夠確定皮膚水蛋白結合狀態和血紅蛋白濃度;並且我們使用 Corneometer 和 Mexameter 的讀數、 DRS 測量結果、以及部分 PASI 分數,進行了交叉驗證分析。我們最後得出結論,DRS量測方法可有效補強現有皮膚電容/反射率測量系統和 PASI 評分系統的量測結果,以實現更有效和客觀的臨床乾癬嚴重程度評估。

  • 23. Fully used reliable data and attention consistency for semi-supervised learning.

    Chang, J.-H., & Weng, H.-C. (2022). Knowledge-Based Systems , 108837. Read this article

    Large labeled datasets represent human labor’s costly consumption of resources. Therefore, semi-supervised learning leverages a large amount of unlabeled data to improve the training results in limited labels. Many methods of semi-supervised learning utilize diverse data augmentations to improve model learning and the classification rule from these changes, requiring models to spend a lot of time to adapt to the changes. Besides, reducing the noise in trained unlabeled data is also an issue that is often discussed in semi-supervised learning so that the inference from error predictions can be reduced. It may define that the data, of which the probability predicted from the model is higher than a threshold, as confident and then only train on those high-confidence unlabeled data so that the model avoids the influence from deviation of the error caused by unlabeled data predictions. However, it also leads to the fact that many unlabeled data cannot be effectively used. Thus, this study proposes a semi-supervised framework, including Attention Consistency (AC) and One Supervised (OS) algorithms, which improves efficiency and performance of the model learning by guiding the model to pay attention to classified features and judging whether the model cannot be effectively trained in existing reliable data. This way, the model fully uses unlabeled data to train. The experiment results and comparisons show that similar results can be reached using other methods within a shorter training process. This paper also analyzes the distribution of feature results and proposes a new measurement to find out distribution information.
    Keywords: Deep learning, Semi-supervised learning, Attention consistency, Reliable data

    充分使用可靠數據和注意力一致性進行半監督學習
    大型標記數據集代表了人類勞動力對資源的高成本消耗。因此,半監督學習利用大量未標記的數據來改善有限標籤的訓練結果。許多半監督學習方法利用不同的數據增強來改進模型學習和這些變化的分類規則,需要模型花費大量時間來適應這些變化。此外,減少訓練的未標記數據中的噪聲也是半監督學習中經常討論的問題,從而可以減少錯誤的預測推斷。可以將模型預測的概率高於某個閾值定義為置信度,然後只對那些置信度高的未標註數據進行訓練,從而避免模型因未標註數據導致的誤差偏差影響預測。然而,這也導致許多未標記的數據無法被有效使用。因此,本研究提出了一種半監督框架,包括注意力一致性Attention Consistency (AC) 和單監督One Supervised (OS) 算法,通過引導模型注意分類特徵並判斷模型是否不能識別來提高模型學習的效率和性能且在現有的可靠數據中得到有效的培訓。如此一來,模型完全使用未標記的數據進行訓練。實驗結果和比較表明,使用其他方法可以在較短的訓練過程中達到類似的結果。本文還分析了特徵結果的分佈,並提出了一種新的度量來找出分佈資訊。

  • 24. Healing of Vertebral Compression Fractures in the Elderly after Percutaneous Vertebroplasty—An Analysis of New Bone Formation and Sagittal Alignment in a 3-Year Follow-Up.

    Kuo, Y.-R., Cheng, T.-A., Chou, P.-H., Liu, Y.-F., Chang, C.-J., Chuang, C.-F., Su, P.-F., Lin, R.-M., & Lin, C.-L. (2022). Journal of Clinical Medicine, 11(3), 708. Read this article

    Background: Vertebral compression fractures, resulting in significant pain and disability, commonly occur in elderly osteoporotic patients. However, the current literature lacks long-term follow-up information related to image parameters and bone formation following vertebroplasty.Purpose: To evaluate new bone formation after vertebroplasty and the long-term effect of vertebroplasty.Methods: A total of 157 patients with new osteoporotic compression fractures who underwent vertebroplasty were retrospectively analyzed. The image parameters, including wedge angles, compression ratios, global alignment, and new bone formation, were recorded before and after vertebroplasty up to three years postoperatively.Results: The wedge angle improved and was maintained for 12 months. The compression ratios also improved but gradually deteriorated during the follow-up period. New bone formation was found in 40% of the patients at 36 months, and the multivariate analysis showed that this might have been related to the correction of the anterior compression ratio. Conclusions: Vertebroplasty significantly restored the wedge angles and compression ratios up to one year postoperatively, and new bone formation was noted on plain radiographs, which increased over time. Last, the restoration of vertebral parameters may contribute to new bone formation.

    背景:脊椎椎體壓迫性骨折多見於老年骨質疏鬆患者,可能導致嚴重的疼痛和殘疾。然而對於使用椎體成型術治療脊椎椎體壓迫性骨折後,長期的影像與椎體內新生骨形成的情形,目前仍無足夠文獻佐證。目的:評估椎體成型術後,脊椎骨癒合情形與在長期追蹤X光影像上的改善幅度。方法:針對157例過去因骨質疏鬆相關之脊椎椎體壓迫性骨折患者,接受椎體成型術後進行影像學的回顧性分析。將經椎體成型術患者,術前及術後追蹤的X光影像分階段檢視,依序從術前片至術後三年的影像,影像分析內容包括椎體楔狀角、壓迫比率、整體排列和新生骨之生長比率。結果:經椎體成型術後椎體楔狀角得到改善,並維持了12個月。術後椎體壓迫比率也有所改善,但在分析術前至術後三年的影像,觀察到壓迫比率有隨時間惡化的跡象。40% 的患者在手術後36 個月時發現新生骨形成,多變量分析顯示這可能與矯正前壓迫比率有關。結論:椎體成形術顯著恢復了椎體楔狀角和術後椎體壓迫比率,且時間可達一年之久;另外透過影像可觀察到新生骨的形成,隨著時間的推移而增加。最後,椎體參數的改善幅度可能與骨癒合情形有相關性。

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