Chu, S.-Y., Wu, M.-J., Yeh, T.-H., Lee, C.-T., & Lee, H.-Y. (2023). Nanomaterials, 13(6), 1064. Read this article

This study utilized a low-cost hydrothermal method to synthesize gallium oxide hydroxide (GaOOH) nanorods and adopted a high-temperature annealing processes to develop nitrogen dioxide (NO2) gas sensors based on gallium oxide (Ga2O3) nanorods. To achieve a high surface-to-volume ratio of GaOOH nanorods, optimization methods were proposed in this study, including optimizing the thickness of the tin oxide (SnO2) seed layer and the precursor concentrations in the hydrothermal synthesis. In addition, GaOOH nanorods could cause dehydrogenation through annealing process to transform into Ga2O3 nanorods and increased the amount of oxygen vacancy. The optimal surface-to-volume ratio of GaOOH nanorods was obtained by using a 50 nm seed layer and a precursor concentration ratio of Ga(NO3)3·9H2O/HMT of 12 mM/10 mM in the hydrothermal synthesis. Furthermore, the NO2 gas sensors with 400 °C-annealed Ga2O3 nanorod sensing membranes exhibited excellent gas sensing performance. The responsivity was 1184.6% and response and recovery times were 63.6 s and 135.7 s, respectively, under a NO2 concentration of 10 ppm. The sensor was capable of detecting NO2 concentration as low as 100 ppb, with a responsivity of 34.2%. Due to its low-cost production and excellent sensing performance, Ga2O3 nanorods hold great potential for applications in NO2 gas sensors.

本研究利用低成本水熱法合成氫氧氧鎵(GaOOH)奈米柱並進行熱退火處理以開發氧化鎵(Ga2O3)奈米柱之二氧化氮(NO2)氣體感測器。為了實現高比表面積的氫氧氧鎵奈米柱，本研究提出之優化方式包括氧化錫(SnO2)晶種層的厚度調整以及水熱合成法之前驅物濃度最佳化。此外，研究證實GaOOH奈米柱可以通過熱退火製程使其進行脫氫反應以轉化為氧化鎵奈米柱，並增加其氧空缺含量。研究結果顯示，使用50 nm之晶種層與Ga(NO3)3·9H2O/HMT濃度為12 mM/10 mM之水熱合成法前驅物濃度比，可獲得最佳比表面積氫氧氧鎵奈米柱。此外，氧化鎵奈米柱經400 ℃熱退火處理後所製備而成之二氧化氮氣體感測器具有最佳的特性，在10 ppm的二氧化氮濃度下，其響應度為1184.6%，響應時間為63.6秒，恢復時間為135.7秒，並且可以檢測最低為100 ppb的二氧化氮濃度，其響應度為34.2%，表現出優秀的氣體感測性能。因此，由於其低成本生產和優異的感測性能，氧化鎵奈米柱在二氧化氮氣體感測器中具有極高的應用前景。

Chen, H.-H., Lin, C.-L., & Chang, C.-H. (2023). Bioengineering, 10(2), 228. Read this article

Neurodegenerative diseases like Parkinson's affect motor functions, resulting in abnormal movements. These symptoms, including tremors and hand movement disorders, can be subtle and vary daily, making evaluating the disease during a short clinical session challenging. To address the issue, this study presents an approach for detecting human micromotion using Wi-Fi channel state information, enabling home health monitoring and examination in regular-sized rooms. The proposed method was tested on three types of motion, and the results demonstrated that micromotion could be accurately captured at multiple locations within the experimental environment. The computer algorithm achieved an average accuracy of 90.9% (single Wi-Fi link) to 95.7% (multiple Wi-Fi links) in computing the frequency and duration of simulated hand tremors.

神經退化性疾病，如巴金森病，會影響動作功能，導致運動異常。這些症狀包括顫抖和手部運動障礙等，在每日生活中細微起伏，亦隨著藥效波動產生變化，故醫師在短暫問診中要準確評估病況有其挑戰性。為解決此問題，本研究提出了一種利用Wi-Fi通道狀態信息監測微小手部動作的方法，能夠在常規大小的房間中進行居家健康監測。經由三種動作類型的測試，顯示本方法在實驗環境中的各個位置上可準確捕捉到微小動作。本研究開發的電腦演算法在偵測模擬手部顫抖的頻率和持續時間的平均準確率為90.9％（單一Wi-Fi收發對）至95.7％（多個Wi-Fi收發對）。

Ho, Y.-R., Chen, B.-Y., & Li, C.-M. (2023). BMC Medical Education, 23(1), 173. Read this article

In medicine, critical thinking is required for managing and tolerating medical uncertainty, as well as solving professional problems and treating diseases. However, the core of Confucianism, teacher-centered and exam-oriented settings in middle and high school education may pose challenges to developing critical thinking in Han Chinese or Taiwanese students. Thus, how to guide students with less stable foundations of critical thinking might require more approach. Almost all healthcare students must complete a biochemistry laboratory course as part of their basic science training. Thus, we aimed to train students to develop critical thinking in the biochemistry laboratory course by using learning sheets and teacher guidance based on the Socratic method and questioning. We recruited second-year students from a medical college, of whom 32 had medical science and biotechnology majors (MSB), 27 had pharmaceutical science majors (PS), and 85 were medical undergraduate (MU) students. Clarity and logic dimensions were identified as the key elements to facilitate the development of critical thinking skills through learning sheets and teacher guidance in students across all three different healthcare majors. The results showed that metacognitive monitoring via Socratic questioning learning sheets have demonstrated potential encourage students to develop critical thinking skills in all dimensions. Another unique contribution of current study was present the heterogeneous learning patterns and progress trajectories of clarity and logic dimensions within classes.

批判性思考是臨床上面對醫學的不確定性，甚至專業問題解決與疾病的診治都需要的技能。然而依據儒家的思維，以教師為中心、考試導向的初中和高中教育環境下，對華人或台灣學生批判性思維的發展確是挑戰。本研究目的在藉由蘇格拉底方法與提問理論，於生化實驗課程中，透過學習單設計和教師引導，培養學生的批判性思考技能。研究對象包括醫技(32人)、藥學(27人)、醫學(85人)。透過蘇格拉底式提問的學習單並進行後設認知的監測分析，顯示此模式可有效地提升學生批判性思考各個面向的表現。其中清晰度和邏輯面相是所有科系學生的關鍵要素。此外研究另一個重要貢獻是提出了異質性學習模式的成果，以及各班級清晰度與邏輯維度的進步軌跡。

Chen, A. E., Xia, X.-Q., Hong, J.-S., & Chen, K.-R. (2023). Nanomaterials, 13(1), 61. Read this article

Light funneling determines how enhanced energy flows into subwavelength slits. In contrast to the previous research on oblique incident light, this study reveals that light funneling in the slits can be highly asymmetric, even at small angles. This mechanism is explained by polarized fields and charges, which are induced using Poynting vectors. It is shown that when light is obliquely incident to the slits perforated in a perfect electric conductor, asymmetrical fields and charges accumulate at the upper apex corners of the left (right) sides. When light is incident from the left (right) side, more (less) induced fields and charges accumulate in the left (right) slit corner so that the funneling width, area, and energy flow at the left (right) side increases (decreases).

光漏斗效應決定了增強能量如何流入次波長狹縫。這項研究揭示了狹縫中的光漏斗在小角度入射下可能是高度不對稱的。這種機制可以通過極化場和電荷以及波印廷向量來解釋。結果顯示，當光線斜向入射完美導體中的狹縫時，不對稱的極化電荷分別累積在左（右）邊的轉角上。當光從左側入射時，會有較多（較少）的電荷累積在左（右）邊 狹縫的轉角，因此左（右）邊的漏斗寬度、面積和能量流增加（減少）。

Cheng, P.-N., Sun, H.-Y., Feng, I. C., Wang, S.-T., Chiu, Y.-C., Chiu, H.-C., Chien, S.-C., & Young, K.-C. (2023). Journal of Virus Eradication, 9(1), 100318. Read this article

Introduction: Hepatitis C (HCV) is associated with extra-hepatic involvment, morbidity as well as metabolic changes. Whether these might be reversible if sustained virologic response (SVR) is achieved by direct-acting antiviral (DAA) therapy remains unknown.Methods: Chronic hepatitis C (CHC) individuals receiving DAA treatment with SVR were compared to those who underwent spontaneous clearance (SC) of HCV infection at the 2-year follow-up. Plasma oxidative stress markers (oxidized low-density lipoprotein (oxLDL), 8-hydroxy-2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and ischemia-modified albumin (IMA)) as well as progression of liver fibrosis were evaluated.Results: Compared to SC individuals, those in the CHC group exhibited at baseline higher levels of oxLDL, 8-OHdG and IMA but not of MDA. In the SC group, 8-OHdG levels were elevated at 2-year post-SVR (p =0.0409), while the DAA-treated CHC group showed decrease in oxLDL (p < 0.0001) and 8-OHdG (p = 0.0255) levels, approaching those of the SC group, but increased MDA (p = 0.0055) levels. Additionally, oxLDL levels were positively correlated with liver stiffness measurements at SVR (p = 0.017) and at 1 year post- SVR (p = 0.002).Conclusions: Plasma oxLDL showed post-SVR normalization after clearance of HCV viremia with DAAs and was associated with levels of hepatic fibrosis.

研究背景:
C型肝炎與肝外受累及代謝變化有關。這些變化是否能藉由直接抗病毒藥物(DAA)療程治療達到持續性病毒反應(SVR)的情況下逆轉仍然未知。
研究方法：
比較接受DAA療程且達到SVR追蹤兩年的慢性C型肝炎病人與自發性清除C型肝炎病毒且追蹤兩年的自願者血漿中氧化壓力標誌物（氧化低密度脂蛋白 (oxLDL)、8-羥基去氧鳥苷 (8-OHdG)、丙二醛 (MDA) 和缺氧修飾白蛋白 (IMA)以及肝纖維化的進展。
研究結果：
與SC組別相比，在CHC 組別中的個體在未接受DAA治療時oxLDL、8-OHdG 和 IMA有更高的表現量；但MDA表現並無差異。在 SC 組別中，8-OHdG 表現量在 SVR 2 年後有升高的趨勢 (p = 0.0409)，而 接受DAA 治療的 CHC 組別中顯示 oxLDL (p < 0.0001) 和 8-OHdG (p = 0.0255) 的表現量下降，且表現量與SC 組相近，但增MDA (p = 0.0055) 的表現量增加。此外，oxLDL 表現量與 SVR (p = 0.017) 和 SVR 1 年後 (p = 0.002) 的肝臟硬度測量值呈正相關。
研究結論:
DAAs清除 HCV 病毒血症後，血漿 oxLDL 的表現量在 SVR 後呈現正常表現且和肝纖維化水平相關。

Li, Y.-C., Wu, C.-H., Le, T. H., Yuan, Q., Huang, L., Chen, G.-F., Yang, M.-L., Lam, S.-H., Hung, H.-Y., Sun, H., Wu, Y.-H., Kuo, P.-C., & Wu, T.-S. (2023). International Journal of Molecular Sciences, 24(14), 11272. Read this article

A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.

之前已報導的1H-NMR方法可以對麻黃類生物鹼進行定量，然而仍然存在一些缺點。本研究對因乙醚的雜質而產生的環化衍生物進行了鑑定，改用苯作為較佳的萃取溶劑，並通過2D NMR的使用確認了各個麻黃類生物鹼的位置。因而修改所得的1H-NMR方法對麻黃類生物鹼的定量更具有專一性。利用此方法分析收集到的20個麻黃樣品，依其結果可分為三類：（一）類草麻黃物種；（二）類中麻黃物種；（三）其他（低生物鹼含量）。 結果表明，麻黃鹼和偽麻黃鹼是麻黃屬植物中的主要生物鹼，但其濃度因植物種類和採集地點的不同而存在較大差異。

Pan, S.-C., Lai, C.-H., Vu, V.-T., Vu, C.-A., Huang, C.-J., Cheng, C.-M., & Chen, W.-Y. (2023). International Journal of Molecular Sciences, 24(14), 9822. Read this article

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. We developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis. We isolated and then quantitatively examined exosomal miR-21 in wound fluids. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.

利用外泌體小分子核糖核酸21型來預測傷口的預後已知資料顯示小分子核糖核酸在傷口癒合扮演重要的角色，外泌體中的小分子核糖核酸已知可利用來診斷疾病的嚴重度。然而，目前尚不清楚小分子核糖核酸21型在傷口扮演何種角色。我們研發一種紙基微流體外泌體小分子核糖核酸21型的分離器，這個方法可快速分離傷口中的外泌體小分子核糖核酸21型，利用這樣的方式可預測傷口的預後。結果顯示8個癒合良好傷口的外泌體小分子核糖核酸21型較低，4個癒合差的傷口外泌體小分子核糖核酸21型較高，證實外泌體小分子核糖核酸21型可用來預測傷口的預後。

Huang, M.-S., Cheng, H.-T., & Hsu, S.-W. (2023). Nanoscale Advances. Read this article

Silver-based nanocrystals have excellent catalytic performance in various reactions, such as the reduction of 4-nitrophenol. The catalytic performance of nanocrystals varies with serval parameters, including nanocrystal morphology, composition, and plasmoninduced hot electrons around nanocrystals. Here, highly heterogeneous nanocrystals (Au-Ag and Ag2S-Ag nanocrystals) fabricated on polymer films via seed-mediated are used as catalysts for the reduction of 4-nitrophenol, and the effect of the morphology and composition of nanocrystals on the catalytic performance is investigated. These nanocrystals on polymer films exhibit higher reusability (low catalysts loss) in catalytic applications compared to catalysts dispersed freely in the reaction solution. The excellent catalyst performance of these heterogeneous nanocrystals is attributed to their high surface area/volume ratio (flower-like nanocrystal) and strong synergistic effect (cage-like nanocrystals). These nanocrystals with special morphologies and composites showed higher catalytic performance (higher reactivity at lower catalysts contents) than silver-based nanocrystals reported in the literature. Due to the excellent plasmonic properties of Ag nanocrystals, the catalytic performance of these nanocrystals can be further enhanced by generating hot electrons around the nanocrystals under irradiation. These results demonstrated that by carefully controlling the morphology and composition of nanocrystals, it is possible to design and fabricate excellent catalysts for various reactions.

銀基奈米晶體在各種反應中具有優異的催化性能，例如 4-硝基苯酚的還原。奈米 晶體的催化性能隨一些參數的變化而變化，包括奈米晶體的形態、組成和奈米晶 體周圍電漿子誘導的熱電子。這裡，通過晶種介導在高分子薄膜上製備的高度非 均質奈米晶體（Au-Ag 和 Ag2S-Ag 奈米晶體）用作 4-硝基苯酚還原之觸媒，並對 奈米晶體的形態和組成對催化性能的影響進行研究。 與自由分散在反應溶液中 的觸媒相比，固定於高分子薄膜上的奈米晶體做為觸媒中表現出更高的可再使用 性（低觸媒回收損失率）。 這些非均質奈米晶體優異的催化劑性可歸因於它們的 高表面積/體積比（花狀奈米晶體）和強的協同效應（籠狀奈米晶體）。 這些具有 特殊形態的奈米晶體比文獻報導的銀基奈米晶體表現出更佳的催化性能（在較低 觸媒含量下具有更高的反應活性）。 由於銀奈米晶體具有優異的電漿子之特性， 這些奈米晶體的催化性能可以在外照光源下，使奈米晶體周圍產生熱電子來進一 步增強催化性能。 這些結果表明通過仔細控制奈米晶體的形態和組成，可以設 計和製造出用於各種反應的優異觸媒。

Pang, H.-H., Huang, C.-Y., Chen, P.-Y., Li, N.-S., Hsu, Y.-P., Wu, J.-K., Fan, H.-F., Wei, K.-C., & Yang, H.-W. (2023). ACS Nano, 17(11), 10407-10422. Read this article

Glioblastomas (GBMs) often resist radiotherapy, with many recurring post-treatment. Enhancing radiotherapy via gene-silencing has thus gained interest. However, challenges in consistent RNA loading in nanoparticles hinder clinical application. We've bioengineered bacteriophage particles with a three-way junction (b-3WJ) RNA scaffold for targeting radioresistant GBM genes. In vitro, the b-3WJ RNA cleavage by Dicer enzyme is trackable via fluorescence microscopy. Moreover, TrQβ@b-3WJ effectively silences both EGFR and IKKα genes, inhibiting the NF-κB pathway and DNA repair. Utilizing convection-enhanced delivery (CED) for TrQβ@b-3WJ, followed by 2Gy X-ray, the median survival extended to over 60 days, compared to just 31 days in the standard 2Gy X-ray group. This highlights RNAi-based strategies' potential and CED's efficacy in enhancing radiotherapy for GBMs without systemic toxicity.

由於膠質母細胞瘤 (GBMs) 常常對放射治療產生抗性，許多病患在化療及放射治療後仍常復發。因此，透過基因沉默來增強放射治療引起了眾多關注。然而，精確調控奈米顆粒中的組成與 RNA 裝載量的困難性導致 RNA 治療產品之間存在批次間變異，這大大限制了其在臨床的應用轉化。在本研究中，我們對噬菌體顆粒進行生物基因工程修改，設計了一種三向接頭 (b-3WJ) RNA骨架，該骨架包含兩個 siRNA/miRNA 序列和一個發光適體，用於靜默放射抗性 GBM 細胞中的基因以降低 GBM 細胞放射抗性。體外試驗結果顯示，使用螢光顯微鏡可實時監測由 Dicer 酶對新設計的 b-3WJ RNA 的切割情況，且 TrQβ@b-3WJ 可同時有效靜默了 EGFR 和 IKKα 基因，進而抑制了 NF-κB 信號傳導途徑，降低 DNA 的修復能力。透過對流增強遞送 (CED) 方式投遞 TrQβ@b-3WJ，隨後進行 2Gy 的低劑量 X 射線照射，結果顯示與僅接受 2Gy X 射線照射的對照組相比，中位生存時間延長到超過 60 天 (對照組中位生存期：31天)。總之，這項研究的結果對於RNAi為基礎的遺傳治療策略設計具有關鍵意義，而CED技術作為一種有效的藥物遞送系統，有助於增強對 GBM 的放療效果並且大幅降低全身性毒性。

Yang, F.-L., Chen, Y.-A., Premlata, A. R., & Wei, H.-H. (2023). Journal of Fluid Mechanics, 967, A29, Article A29. Read this article

A stick-slip asymmetry can break the symmetry of the local hydrodynamic force distribution on the surface of an otherwise no-slip or uniform-slip particle. Here we use the Lorentz reciprocal theorem to demonstrate that such asymmetry, even in a small amount, can completely change the swimming characteristics of a self-propelled spherical squirmer, making its behavior markedly different than a no-slip or uniform-slip squirmer. We find that the swimming velocity U of a stick-slip squirmer can be driven alone by a symmetric extensile/contractile squirming from the B2 mode that commonly provides a stresslet, capable of reversing the swimming direction of the squirmer. A symmetric force dipole, namely stresslet S, can also be generated solely by a unidirectional diverging and converging squirming from the B1 mode that provides the thrust for the swimming, which can invert the stresslet of the squirmer from extensile type to contractile type or vice versa. When these two squirming modes are executing together, both U and S can be enhanced or diminished due to the interplays between asymmetric squirming forces generated by these two modes, depending on the stick-slip partition and orientation. These distinctive features arising from stick-slip asymmetry can not only be made geometrically tunable for steering the motion of a squirmer, but also provide new means for making efficient artificial microswimmers using catalytic Janus particles.

黏滑不對稱性可以破壞無滑移或均勻滑移粒子表面上的局部流體力學受力分佈的對稱性。我們使用洛倫茨互易定理來證明，即使是微小的黏滑不對稱性也可以完全改變球形自滑粒子的自泳動特性，使其表徵與無滑移或均勻滑移的自滑粒子明顯不同。我們發現，黏滑自滑粒子的泳動速度 U 可單獨由慣常提供應力子的 B2 模式的對稱伸展/收縮方式來驅動，該模式能夠反轉自泳動方向。而對稱的力偶，即應力子 S，也可以僅通過提供泳動所需推力的單向滑游B1模式來生成，可以將自滑粒子的應力子從伸展型轉變為收縮型，反之亦然。當這兩種自滑模式一起執行時，由於這兩種模式產生的不對稱滑泳力之間的相互作用，U 和 S 可能增強或減弱。由黏滑不對稱性引起的這些獨特性質不僅可藉幾何方式調控自泳動粒子的運動，還可能為使用兩面催化粒子製備高效的人工微米自游動機帶來新的方案。

Tu, H.-N., Shan, T.-H., Wu, Y.-C., Shen, P.-H., Wu, T.-Y., Lin, W.-L., Yang-Kao, Y.-H., & Cheng, C.-L. (2023). Journal of Medical Systems, 47(1), 52. Read this article

Medication errors can have severe consequences and threaten patient safety. The patient safety-related benefits of automated dispensing cabinets (ADCs) have been reported by several previous studies, including a reduction in medication errors in intensive care units (ICUs) and emergency departments. However, the benefits of ADCs need to be assessed, given the different healthcare practice models. This study aimed to compare the rates of medication errors, including prescription, dispensing, and administrative, before and after using ADCs in intensive care units. The prescription, dispensing, and administrative error data before and after the adoption of ADCs were retrospectively collected from the medication error report system. The severity of medication errors was classified according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines. The study outcome was the rate of medication errors. After the adoption of ADCs in the intensive care units, the rates of prescription and dispensing errors reduced from 3.03 to 1.75 per 100,000 prescriptions and 3.87 to 0 per 100,000 dispensations, respectively. The administrative error rate decreased from 0.046 to 0.026%. The ADCs decreased National Coordinating Council for Medication Error Reporting and Prevention category B and D errors by 75% and category C errors by 43%. To improve medication safety, multidisciplinary collaboration and strategies, such as the use of automated dispensing cabinets, education, and training programs from a systems perspective, are warranted.

用藥錯誤可能引發嚴重後果，危及病人安全。先前多項研究已指出自動調劑要貴（Automated dispensing cabinets, ADCs）對於病人安全的正面效益，尤其在重症加護病房及急診部門能夠顯著減少用藥錯誤。然而，鑒於各種醫療實踐模式的差異，我們需要深入評估自動調劑藥櫃在台灣醫療環境中的實際效益。本研究的目的是比較在重症加護病房使用自動調劑藥櫃前後的用藥錯誤率，涵蓋處方、調劑及給藥等方面的錯誤。我們從用藥錯誤報告系統中回顧性地蒐集了使用自動調劑藥櫃前後的相關錯誤事件數據。所有的用藥錯誤嚴重性都依照國家藥物錯誤報告和預防協調委員會的指南進行分類。研究結果發現，在重症加護病房採用自動調劑藥櫃後，每10萬份處方和每10萬次調劑中的錯誤率從3.03和3.87分別降到1.75和0。而給藥錯誤率也從0.046%減少到0.026%。此外，自動調劑藥櫃使得按照國家藥物錯誤報告和預防協調委員會分類的B類嚴重度和D類嚴重度錯誤減少了75%，C類嚴重度錯誤則減少了43%。為了進一步提高藥物的使用安全，我們應該結合跨科部的合作，並採取加強教育與系統化培訓等策略。

Chen, C.-F., Fu, C., & Chen, Y.-C. (2023). Transportation Research Part A: Policy and Practice, 47(1), 52. Read this article

Mobility-as-a-Service (MaaS) provides travelers with a single digital travel platform that integrates information, booking, and payment with considerable discounts. Existing MaaS studies mainly focus on commuters’ daily mobility instead of tourists’ mobility during their stay at destinations. However, the tourist market is a potential but neglected MaaS market. To explore tourist preference for MaaS bundled services, this research examines the preference heterogeneity of tourist-specific MaaS bundles among 491 Taiwanese tourists by using the latent class choice model. The choice experiments are designed by seven MaaS bundle attributes, including public transport, shared bike, shared e-moped, shared car, shopping discount, attraction ticket discount and price. Three tourist classes, namely, MaaS Skeptics, MaaS Supporters, and MaaS Enthusiasts, are identified based upon three attitudinal latent variables (hedonic motivation, Attitude toward MaaS and mobile application factor) as well as socioeconomic characteristics. The results provided evidence of a tourist-specific MaaS market and preference heterogeneity among various tourist classes in Taiwan. Class profiles and scenario analyses of pro-MaaS propensity for three classes were conducted to provide deeper insights into preference variations.

交通行動服務方案提供旅運者一個單一的數位旅運平臺用來整合資訊、訂票以及支付具有折扣的整合方案。目前大部分的交通行動服務方案都是針對通勤者的旅運需求進行探討，但是對觀光客在目的地停留期間的旅運需求之了解仍為研究之缺口。實際上針對觀光客旅運需求所提供的交通行動方案，乃是MaaS的另外一個值得重視的利基市場。為了分析觀光客對觀光MaaS組合服務方案的需求偏好，本研究以臺灣重要觀光目的地(高雄駁二文創園區)為研究情境，利用潛在類別選擇模型（Latent Class Choice Model, LCCM）分析觀光客敘述性偏好問卷資料，以瞭解觀光客對觀光MaaS方案所重視的屬性，並透過潛在變數所得的分群，探討不同分群對需求偏好之差異，已達成對偏好異質性的掌握。選擇實驗所考慮的MaaS組合運具屬性包括公共運輸、共享單車、共享電動機車、購物折扣、觀光景點入門費折扣、以及方案價格。透過三項潛在變數（享樂動機、對MaaS的態度、及行動APP的使用態度等）進行受訪者之分群，得到3個觀光客分群，包括MaaS懷疑者、MaaS支持者、及MaaS擁護者。透過對此3個分群進行受訪者組成分析，可以提供MaaS方案行銷策略重要的訊息，進而設計適合各分群觀光客需要的組合方案。

Tsai, H.-W., Chen, Y.-L., Wang, C.-I., Hsieh, C. C., Lin, Y.-H., Chu, P.-M., Wu, Y.-H., Huang, Y.-C., & Chen, C.-Y. (2023). Cancer Cell Internationall, 23(1), 42. Read this article

Background:
Hepatocellular carcinoma (HCC) accounts for almost 80% of all liver cancer cases and is the sixth most common cancer and the second most common cause of cancer-related death worldwide. The survival rate of sorafenib-treated advanced HCC patients is still unsatisfactory. Unfortunately, no useful biomarkers have been verified to predict sorafenib efficacy in HCC.
Results: We assessed a sorafenib resistance-related microarray dataset and found that anterior gradient 2 (AGR2) is highly associated with overall and recurrence-free survival and with several clinical parameters in HCC. However, the mechanisms underlying the role of AGR2 in sorafenib resistance and HCC progression remain unknown. We found that sorafenib induces AGR2 secretion via posttranslational modification and that AGR2 plays a critical role in sorafenib-regulated cell viability and endoplasmic reticulum (ER) stress and induces apoptosis in sorafenib-sensitive cells. In sorafenib-sensitive cells, sorafenib downregulates intracellular AGR2 and conversely induces AGR2 secretion, which suppresses its regulation of ER stress and cell survival. In contrast, AGR2 is highly intracellularly expressed in sorafenib-resistant cells, which supports ER homeostasis and cell survival. We suggest that AGR2 regulates ER stress to influence HCC progression and sorafenib resistance.
Conclusions: This is the first study to report that AGR2 can modulate ER homeostasis via the IRE1α-XBP1 cascade to regulate HCC progression and sorafenib resistance. Elucidation of the predictive value of AGR2 and its molecular and cellular mechanisms in sorafenib resistance could provide additional options for HCC treatment.

肝癌為全世界發生率第六且死亡率第二的癌症，其中肝細胞癌占了百分之八十。蕾莎瓦(sorafenib)增加後期肝細胞癌病人的存活時間，依然不理想，且多種副作用及產生蕾莎瓦抗藥性等現象被發現。可惜目前為止，沒有有效的生物標記可預測肝細胞癌病人對蕾莎瓦治療的效果。為達成此目標，我們將肝細胞癌對蕾莎瓦有抗藥性的細胞資料庫以及Roessler Liver microarray作分析，找尋與肝細胞癌發展及存活率有關的重要分子。目前為止，初步發現由蕾莎瓦有抗藥性的細胞資料庫中，挑選出前梯度蛋白2 (AGR2)與肝細胞癌病人的整體存活率及無復發存活率有高度相關，且與多種臨床因子有高度關聯。蕾莎瓦可能透過轉譯後修飾的方式促進前梯度蛋白2的分泌，而非轉錄調控的方式，在對蕾莎瓦敏感性的肝細胞癌細胞株中，前梯度蛋白2在蕾莎瓦調節細胞存活率、內質網壓力及促進細胞凋亡過程中，扮演重要角色。我們建立了對蕾莎瓦有抗藥性的細胞株，前梯度蛋白2在抗藥性細胞中高度表現。根據我們初步結果，我們認為前梯度蛋白2在肝細胞癌的發展及對蕾莎瓦的抗藥性，扮演重要角色。因此，我們假設在蕾莎瓦敏感性細胞中，前梯度蛋白2在細胞中含量降低，且增加分泌到細胞外，此現象會降低對內質網壓力的調節及降低細胞的存活率，另一方面，前梯度蛋白2高度表現在對蕾莎瓦有抗藥性細胞中，此現象可增加對內質網壓力的調節，提高細胞存活率。在此計畫中，我們預期前梯度蛋白2會調節肝細胞癌的內質網壓力，進而影響癌細胞的發展及蕾莎瓦的抗藥性。此計畫的完成，對於前梯度蛋白2於蕾莎瓦敏感性及抗藥性細胞中，所扮演的角色會有深入了解，可應用在發展預測性、早期診斷及預後的分子，建立治療肝細胞癌新穎的治療標的分子。

Patra, S. R., Chu, H.-J., & Tatas. (2023). Journal of Hydrology: Regional Studies, 47, 101442. Read this article

This study proposes and evaluates a Long Short-Term Memory (LSTM) model to predict daily fluctuations of regional groundwater patterns using observations across multiple monitoring wells in Choushui River Alluvial Fan located in Central Taiwan. Global models calibrated over all monitoring well data were compared with the local LSTM models each trained on the local well data for regional groundwater sequential forecast. Spatial assessment showed that the results from the local model were adversely affected when trained on data from coastal wells indicating that these areas require special attention for regional forecasting. Eventually, a fine-tuning through Transfer Learning (TL) scheme was further proposed to show considerable improvements in model performance, and to highlight the potential advantages of synthesizing cross-data information for model training when suffering from hydrogeological heterogeneity in fields.

本研究提出並長短期記憶（LSTM）模型，運用於台灣中部濁水溪沖積扇監測井的觀測結果來預測區域地下水每日變化。根據所有監測井數據校準的全局模型與區域LSTM 模型進行比較，每個模型均根據本地井數據進行訓練，以進行區域地下水預測。當使用沿海井數據進行訓練時，區域模型的結果受到不利影響，這表示這些區域需要特別關注及預測。最終，進一步提出了藉由遷移學習（TL）方案進行微調，可獲取極大的改善。得到模型性能的改進，並強調在受現場水文地質異質性影響之數據也能直接進行模型訓練。

Hsu, H.-C., & Sung, T.-C. (2023). BMC Medical Education, 23(1), 497. Read this article

In a scenario of ongoing changes in the theory and methodology of teaching, student-centered practices are crucial in improving teaching and learning outcomes. This study aimed to evaluate whether the learning styles and attitudes (connected and separate knowing) associated with the curriculum differ among medical students. The research subjects consisted of 43 first- and second-year medical students attending a post-baccalaureate medical education program exclusively for foreign students at a comprehensive university in Kaohsiung City, Taiwan. A self-administered Attitudes Toward Thinking and Learning Survey (ATTLS) was used to assess the differences in learning styles and attitudes among grades, gender, and nationality of these post-baccalaureate medical students. The reliability value of Cronbach Alpha coefficients for all items of ATTLS was 0.93. These medical students reported significantly higher connected knowing styles than separate knowing. The average score of the connected knowing for first-year students taking the "International Health" course is significantly higher than that of second-year students taking the "Population Health and Sustainable Development" course. There is no difference in the separate knowing between these two curricula. The learning styles and attitudes of students participating in the teaching process showed no difference in grade, gender, and nationality. The evidence that there is a significant interaction effect of grade, gender, and nationality examined with the separate knowing, rather than the connected knowing, suggests that this heterogenicity of learning methodology needs to be considered and integrated into future teaching methods.

Keywords:learning styles and attitudes, post-baccalaureate, medical education

對外國學生在學士後醫學教育課程中的學習風格和態度進行分析在不斷變化的教學理論和方法論中，以學生為中心的實踐對改善教學和學習成果至關重要。本研究旨在評估醫學生中與課程相關的學習風格和態度（聯繫求知風格(connected knowing styles)和分離知識求知風格(separate knowing style)）是否有所不同。研究對象包括台灣高雄市一所綜合大學專為外國學生提供的學士後醫學教育課程的43名一年級和二年級醫學生。使用自行填寫的《思維和學習態度調查量表》（ATTLS）來評估這些學士後醫學生在年級、性別和國籍方面的學習風格和態度之間的差異。ATTLS的所有項目的Cronbach Alpha系數的可靠性值為0.93。結果發現，這些醫學生的聯繫求知風格(connected knowing styles)明顯高於分離求知風格(separate knowing style)的。一年級學生在修讀“國際健康”課程時的聯繫求知風格平均分顯著高於修讀“人口健康與可持續發展”課程的二年級學生。在這兩個課程之間的分離知識沒有差異。參與教學過程的學生的學習風格和態度在年級、性別和國籍方面沒有差異。對於分離求知風格而言，年級、性別和國籍的交互作用效應具有顯著性，而不像聯繫求知風格，這表明這種學習方法的多樣性需要納入未來的教學方法中。

Liou, C.-W., Cheng, S.-J., Yao, T.-H., Lai, T.-T., Tsai, Y.-H., Chien, C.-W., Kuo, Y.-L., Chou, S.-H., Hsu, C.-C., & Wu, W.-L. (2023). Brain, Behavior, and Immunity, 113, 104-123. Read this article

Social novelty is a cognitive process that is essential for animals to interact strategically with conspecifics based on their prior experiences. The commensal microbiome in the gut modulates social behavior through various routes, including microbe-derived metabolite signaling. Short-chain fatty acids (SCFAs), metabolites derived from bacterial fermentation in the gastrointestinal tract, have been previously shown to impact host behavior. Herein, we demonstrate that the delivery of SCFAs directly into the brain disrupts social novelty through distinct neuronal populations. We are the first to observe that infusion of SCFAs into the lateral ventricle disrupted social novelty in microbiome-depleted mice without affecting brain inflammatory responses. The deficit in social novelty can be recapitulated by activating calcium/calmodulin-dependent protein kinase II (CaMKII)-labeled neurons in the bed nucleus of the stria terminalis (BNST). Conversely, chemogenetic silencing of the CaMKII-labeled neurons and pharmacological inhibition of fatty acid oxidation in the BNST reversed the SCFAs-induced deficit in social novelty. Our findings suggest that microbial metabolites impact social novelty through a distinct neuron population in the BNST.

社交新穎性對於動物來說是一個必要的認知過程，能幫助動物根據過往經驗，有策略性地與其他同種動物互動。腸道共生細菌能透過多樣的機制調控社交行為，其中包含細菌所產生的代謝產物訊息路徑。從過去的研究發現，細菌在腸道中發酵時所產生的短鏈脂肪酸能影響宿主行為，我們的研究證明在小鼠大腦直接給予短鏈脂肪酸，透過獨特的神經族群降低小鼠的社交新穎性，但不會影響小鼠大腦中的發炎反應。再者，活化紋狀體終床核中鈣離子／鈣調素依賴性蛋白酵素標記的神經元，能在小鼠上重現社交新穎性的缺陷。相反地，利用化學遺傳學抑制紋狀體終床核中鈣離子／鈣調素依賴性蛋白酵素標記神經元，與利用藥理學抑制粒線體脂肪酸的氧化作用，能回復小鼠因為短鏈脂肪酸所導致的社交新穎性缺失。我們的研究證實細菌代謝產物能透過紋狀體終床核中獨特的神經族群，影響小鼠的社交新穎性。

Shih, Y.-C., Chen, W. C., Chen, T.-A. P., & Chang, C.-w. (2023). [Original Research]. Frontiers in Marine Science, 10. Read this article

Since the establishment of the Ocean Affairs Council (OAC) in Taiwan in 2018, ocean governance has reached a new milestone. In 2019, the Ocean Basic Act was enacted, and in 2020, the National Ocean Policy White Paper was published, meaning that Taiwan has specialized ocean authorities, regulations, enforcement units, and relevant mechanisms and policies. The Ocean Conservation Administration (OCA) is also responsible for marine environmental protection and conservation. To ensure good ocean governance, maintain marine resources, and protect the environment, the OCA has recently drafted the Marine Conservation Act for sustainable development. This article mainly reviews, analyzes, and compares Taiwan’s current marine-related laws and regulations and refers to the laws, policies, and mechanisms of other countries to provide suggestions on marine governance and the ongoing draft of the Marine Conservation Act.

2018年臺灣成立"海洋委員會"（OAC）以來，海洋治理邁向新的里程碑。2019 年頒布了《海洋基本法》、2020年政府公布《國家海洋政策白皮書》，這意味著臺灣有了專責的海洋主管機關、法規、執法單位以及相關機制和政策。海洋保育署（OCA）也負責海洋環境保護與保育任務。為確保良好的海洋治理、維護海洋資源、保護環境，海洋保育署最近起草了《海洋保護法》，以促進海洋的永續發展。本文主要回顧、分析和比較臺灣現行的海洋相關法律規範，並參考其他國家的法律、政策和機制，為我國海洋治理和正在起草的《海洋保育法》提供建議。

Hsiao, K.-C., Ruan, S.-Y., Chen, S.-M., Lai, T.-Y., Chan, R.-H., Zhang, Y.-M., Chu, C.-A., Cheng, H.-C., Tsai, H.-W., Tu, Y.-F., Law, B. K., Chang, T.-T., Chow, N.-H., & Chiang, C.-W. (2023). Cell Communication and Signaling, 21(1), 172. Read this article

Colorectal cancer is a leading cause of cancer mortality, which accounts for approximately 10% of cancer-related mortality in Western countries and the incidence of colorectal cancer has increased steadily in the past ten years and has recently become the most common cancer in Taiwan. Although several treatment options are available for patients of colorectal cancer, very limited options of effective therapy are applied for treating the advanced stages of colorectal cancer. Our finding reveals a novel oncogenic mechanism involving the B56γ3 regulatory subunit-containing PP2A in colorectal cancer. PP2A was previously recognized as a tumor suppressor, whereas our current finding indicates that the B56γ3 regulatory subunit can lead PP2A to downregulate p70S6K-mediated negative feedback loop on growth factor signaling, resulting in oncogenic AKT hyper-activation. Our finding suggests that the PP2A-B56γ3/p70S6K signaling module may serve as a therapeutic target to control tumor progression of colorectal cancer.

大腸癌是導致癌症死亡的主要原因，在西方國家約佔癌症相關死亡率的 10%，近十年來，大腸癌的發病率持續上升，已成為台灣最常見的癌症。雖然大腸癌患者可以選擇多種治療方法，但用於治療晚期大腸癌的有效療法非常有限。我們的發現揭示了一種新的致癌機制，涉及大腸癌中含有 B56γ3 調節次單元的 PP2A。 PP2A 以前被認為是一種腫瘤抑制因子，而我們目前的發現顯示，B56γ3 調節次單元可引導 PP2A 下調 p70S6K 介導的生長因子信號傳遞的負反饋環調控而促成致癌性AKT激酶的過度活化。我們的發現闡明，PP2A-B56γ3/p70S6K 信號模組可作為控制大腸癌腫瘤進展的治療標的。

Chen, C.-Y. (2023). Journal of Parallel and Distributed Computing, 182, 104752. Read this article

Coflow is a network abstraction used to represent communication patterns in data centers. The coflow scheduling problem encountered in large data centers is a challenging NP-hard problem. Many previous studies on coflow scheduling mainly focus on the single-core model. However, with the growth of data centers, this single-core model is no longer sufficient. This paper addresses the coflow scheduling problem within heterogeneous parallel networks, which feature an architecture consisting of multiple network cores running in parallel. In this paper, two polynomial-time approximation algorithms are developed for the flow-level scheduling problem and the coflow-level scheduling problem in heterogeneous parallel networks, respectively. For the flow-level scheduling problem, the proposed algorithm achieves an approximation ratio of O(log m/ loglog m) when all coflows are released at arbitrary times, where $m$ represents the number of network cores. On the other hand, in the coflow-level scheduling problem, the proposed algorithm achieves an approximation ratio of O(m(log m/loglog m)^2) when all coflows are released at arbitrary times. Moreover, we propose a heuristic algorithm for the flow-level scheduling problem. Simulation results using synthetic traffic traces validate the performance of our algorithms and show improvements over the previous algorithm.

Coflow是一種用於表示資料中心通訊模式的網路抽象。本論文分別為異質平行網路中的流級排程問題和coflow級排程問題開發了兩種多項式時間近似演算法。對於流級排程問題，所提出的演算法達到O(log m/ loglog m)的近似比，其中m代表網路核心的數量。另一方面，在coflow級排程問題中，所提出的演算法達到O(m(log m/loglog m)^2) 的近似比。

Fang, P.-H., Kuo, P.-L., Wang, Y.-W., Cheng, H.-L., & Chou, W.-Y. (2023). Polymers, 15(11), 2421. Read this article

In this comprehensive study, we meticulously fine-tuned the solid content of polyimide (PI) to strategically enhance the surface properties of the dielectric layer in organic field-effect transistors (OFETs). Our primary objective was to mitigate defect density at the critical interface between the dielectric and the organic semiconductor layer within OFETs. Through this modulation, we achieved significant enhancements in electrical characteristics and overall stability of the OFETs. Notably, a higher solid content of the PI film directly correlated with elevated current stability in the OFET, showcasing a promising avenue for tailored device performance. Leveraging this optimized PI film in organic memory devices demonstrated remarkable attributes, notably improved storage retention and durability. These advancements pave the way for highly stable devices, making them well-suited for integration into future flexible electronic products, thereby fostering the evolution of this technology towards a more sustainable and versatile future.

本研究中，我們調控聚醯亞胺固含量的濃度來修飾有機場效電晶體的介電層，主要目的減少介電層的缺陷密度進而改善元件之電特性和穩定性。從研究成果得知若聚醯亞胺薄膜的固含量越高，其元件的電流穩定性越高。將此薄膜應用於有機記憶元件上，可表現出良好的儲存保持性和耐久性。這些高穩定性元件未來可應用於柔性電子產品上。

Bui-Diem, K., Hung, C.-H., Zhu, G.-C., Tho, N. V., Nguyen-Binh, T., Vu-Tran-Thien, Q., To-Truong, D., Ngo-Thanh, H., & Duong-Quy, S. (2023). Frontiers in Neurology, 14. Read this article

Purpose: In this study, we described “Physical Therapy for Sleep Apnea”, a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea.Methods: The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam, and National Cheng Kung University, Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training.Results: The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea.Conclusion: In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with Obstructive Sleep Apnea.

目的：在這項研究中，我們描述了“睡眠呼吸中止症的物理治療”，這是一款用於對阻塞性睡眠呼吸中止症患者進行居家物理治的智能手機應用程式。方法：該應用程式是由越南胡志明市醫藥大學和台灣國立成功大學聯合創建的。運動訓練計畫是國立成功大學研究小組之前已經發表的。其中包括上呼吸道和呼吸肌訓練以及一般耐力訓練。結果：該應用程式提供視頻和文字教程供患者在家遵循，並提供日程表功能來幫助用戶組織培訓計劃，這可能會提高阻塞性睡眠呼吸中止症患者的居家物理治療的效果。結論：在未來，本研究計劃進行使用者研究和隨機對照試驗，以調查我們的應用程式是否可以使阻塞性睡眠呼吸中止症患者患者受益。

Nakazawa, T., Katayama, N., Utsumi, S., Yamawo, A., & Yamamichi, M. (2023). Frontiers in Ecology and Evolution, 11. Read this article

Mutualism is common in nature and is crucial for population dynamics, community structure, and ecosystem functioning. Studies have recently pointed out that life-history stage structure (e.g., juveniles and adults) is a key factor to better understand the ecological consequences of mutualism (termed stage-structured mutualism). Despite the potential importance, little is known about what kinds of stage-structured mutualism can evolve and when it is likely to occur. Here, we theoretically investigated how a mutualistic partner species should allocate efforts of mutualistic associations for different life-history stages of its host species to maximize its fitness. We assessed the partner’s optimal strategy by using a one host–one partner model with the host’s juvenile-adult stage structure. The results showed that different forms of stage-structured mutualism can evolve, such as juvenile-specialized association, adult-specialized association, and inter-stage partner sharing (i.e., the partner associates with both the juvenile and adult stages of the host) depending on the shape of association trade-off, i.e., how much association with one stage is weakened when the partner strengthens its association with the other stage. In general, stage-specialized association (either juvenile-specialized or adult-specialized association) tends to evolve when being associated with that stage is relatively beneficial. Similarly, adult-specialized association tends to evolve if it is relatively beneficial. Meanwhile, when the association trade-off is weak, inter-stage partner sharing can occur if the mutualistic benefits of juvenile-specific and adult-specific associations are sufficiently large. We also found that when the association trade-off is strong, alternative stable states occur in which either juvenile-specialized or adult-specialized associations evolve depending on the initial trait value. These results suggest that pairwise interspecific mutualism is more complicated than previously thought, implying that we may under- or overestimate the strength of mutualistic interactions when looking at only certain life-history stages. This study provides a conceptual basis for better understanding the mechanisms underlying ontogenetic shifts of mutualistic partners and more complex mutualistic networks mediated by the life-history stages of organisms and their stage-structured interactions.

何時幫助幼體、成體或兩者兼而有之：分析階段結構互利共生的進化模型

互利共生在自然界中很普遍，對種群動態、群落結構，和生態系統運作至關重要。研究指出，生活史階段結構（如幼體和成體）是更好地理解互利共生生態後果的關鍵（階段結構互利共生）。儘管有潛在的重要性，對於什麼階段結構互利共生可以進化及何時發生知之甚少。我們將從理論上研究互利共生夥伴應如何為其宿主的不同生活史階段分配互利共生關係的精力，以最大提高適應性。我們通過一個宿主-一個夥伴模型與宿主的幼體至成體階段結構評估夥伴的最優策略。結果表明，不同形式的階段結構互利共生可以進化，如幼體特定關係、成體特定關係，和階段間夥伴共享（即夥伴與宿主的幼年和成年階段的關係）取決於關係權衡的形式，即當夥伴加強與一階段的關係時，與另一個階段的關係減弱多少。一般來說，階段特定關係（無論幼體或成體）傾向在階段相對有益時進化。當關係權衡較弱，如果幼體和成體特定的互利共生利益足夠大，則可能發生階段間夥伴共享。而當關係權衡較強，會出現替代穩定狀態，其中幼體或成體特定關係會根據初始特徵值進化。我們可能僅觀察到某些生活史階段而錯估了互利共生作用的強度。這項研究是為更好地理解互利共生夥伴個體的轉變機制及生物體的生活史階段結構相互作用介導的複雜互利共生網絡提供概念基礎。

Wong, C.-E., Huang, C.-C., Chuang, M.-T., Lee, P.-H., Chen, L.-Y., Hsu, H.-H., Huang, C.-Y., Md, P., Wang, L.-C., Lee, J.-S., & Md, M. (2023). Int J Surg, 109(9), 2704-2713. Read this article

Background:

Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumours (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counselling.

Material and methods:

This study was a retrospective cohort and quantitative analysis of the literature. The authors introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-centre cohort from 2008 to 2021.

Results:

In total, 17 patients from our single-centre cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumours had the largest CJA, followed by sympathetic tumours, whereas cervical nerve tumours had the smallest CJA (P＜0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO (P＜0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831–0.951) for the CJA to predict vagus NO (P＜0.001). External validation showed an AUC of 0.928 (0.727–0.988) (P＜0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673–0.839), that of the CJA was greater (P=0.011). The cut-off value identified to predict vagus NO was greater than or equal to 100°. Receiver operating characteristic analysis showed an AUC of 0.909 (0.837–0.956) for the CJA to predict cervical NO (P＜0.001), with a cut-off value less than 38.5°.

Conclusions:

A CJA greater than or equal to 100° predicted a vagus NO and a CJA less than 100° predicted a non-vagus NO. Moreover, a CJA less than 38.5 was associated with an increased likelihood of cervical NO.

頸部是周邊神經鞘腫瘤(peripheral nerve sheath tumor)最好發的部位，在這個狹小的空間內，除了左右各有兩條重要的血管外，還有多條重要的神經，包括迷走神經(vagus nerve)、交感神經(sympathetic nerve)、頸神經(spine nerve)；對周邊神經鞘腫瘤的治療，手術切除是唯一的治療方式，但是術中的神經損傷所造成術後神經麻痺是最主要的併發症，因為目前無有效且準確的術前診斷方式來判定腫瘤的來源神經，所以醫師無法有效率和準確地執行術中神經監測，病人也無法在術前得知手術可能危及的神經和相對應的手術風險；為了解決這個臨床治療的難題，我們利用頸部血管、腫瘤、來源神經解剖位置的相對關係提出了一個新的參數: 頸動脈-頸靜脈角(carotid-jugular angle, CJA)，假設這個角度會因為腫瘤的來源神經不同分別有相對應的角度，用以辨別周邊神經鞘腫瘤的來源神經。首先，利用大體老師(cadaveric neck)來建立頸動脈-腫瘤-頸靜脈的示意模型；回顧分析我個人過去自2008年至2021年所有手術案例，利用2010年至2022年文獻中周邊神經鞘腫瘤的影像資料來執行外部驗證，總共分析了院內的17名患者與文獻中的88名患者影像的頸動脈-頸靜脈角，其中53名患者的來源神經為交感神經、45名為迷走神經、7名為頸椎神經根。迷走神經鞘瘤有最大的頸動脈-頸靜脈角，其次為交感神經鞘瘤，頸椎神經根瘤的角度則最小。利用多變量邏輯回歸分析和ROC曲線分析顯示預測迷走神經鞘瘤的截斷值為 ≥1000，預測頸神經根神經鞘瘤的截斷值為 ＜ 8.50。

所以，利用術前的CT或 MRI，當周邊神經鞘腫瘤的頸動脈-頸靜脈角≥1000，可預測為迷走神經鞘瘤，頸動脈-頸靜脈角< 100°且 > 38.50，則可預測為交感神經瘤，頸動脈-頸靜脈角< 38.50則為頸神經鞘瘤，此方法可以簡單而且準確地在術前準斷出腫瘤的來源神經，醫生可以有目標的執行手術和神經監測、病患可以清楚知道可能的併發症，此方法是目前世界上唯一的客觀術前診斷方式。

Chiu, Y.-C., Yeh, M.-C., Wang, C.-H., Chen, Y.-A., Chang, H., Lin, H.-Y., Ho, M.-C., & Lin, S.-M. (2023). Nature Communications, 14(1), 5946. Read this article

The Vibrio α-hemolysin is a β-pore-forming toxin secreted by Vibrio bacteria, crucial for enhancing bacterial infections. In our study on Vibrio campbellii α-hemolysin (VcαHL), we found that its hemolytic activity is significantly elevated under the induction of calcium ions. We further investigated how calcium ions promote the assembly of VcαHL on the cell membrane. Using X-ray crystallography and cryo-electron microscopy, we presented the precursor and assembled structures of VcαHL. Notably, VcαHL contains a calcium-binding site, playing a pivotal role in its activation. These novel findings provide a new direction for therapeutic strategies against Vibrio infections.

弧菌α溶血素是由弧菌所分泌的β-孔形成毒素，對於加劇細菌感染極為重要。我們研究了坎氏弧菌α溶血素（VcαHL）的生化功能，發現其溶血活性在鈣離子的誘導下明顯提升。我們更深入探討鈣離子如何促使VcαHL在細胞膜上組裝成孔。透過X射線晶體學與冷凍電子顯微鏡技術，我們解析了VcαHL的前驅體與組裝結構。特別的是，VcαHL中含有一個鈣離子結合區域，對於毒素組裝扮演了關鍵角色。這些新的發現為針對弧菌感染的治療策略提供了新的方向。

Chen, C.-Y., Lee, C.-H., Lin, H.-W., Lin, S.-H., & Li, Y.-H. (2023). Scientific Reports, 13(1), 6941. Read this article

Infection is a common cause of hospitalization in patients with heart failure (HF). The impact of infection on long term cardiovascular outcome in HF is not well studied. The aim of this study was to compare the long-term risk of major adverse cardiovascular events (MACE) in HF patients with or without prior hospitalization for infection. From 2009 to 2015, 310,485 patients with their first HF admissions were enrolled from the Taiwan National Health Insurance Research Database. Among the patients, those with readmission due to infection within one year after HF discharge were defined as infection group and those without any infection admission were controls. The propensity score matching method was used to balance covariates between the two groups. In a mean follow-up time of 4.29 ± 2.92 years, 86.19% of patients in the infection group and 63.63% of patients in the control group had MACE. Multivariate Cox proportional hazards analysis showed the infection group had a higher risk of MACE, including all-cause mortality, myocardial infarction, stroke and hospitalization for HF. In conclusion, many HF patients discharged from the hospital experienced acute infection that required readmission. The patients had worse cardiovascular outcome after readmission for infectious disease compared to those without any infection.

感染是心衰竭（HF）患者住院的常見原因之一。感染對心衰竭患者長期心血管結果的影響尚未充分研究。本研究的目的是比較心衰竭患者先前因感染住院對其發生主要不良心血管事件(MACE)的長期風險。我們由2009年至2015年，台灣全民健康保險研究資料庫收錄了310,485名首次因心衰竭入院的病人。患者中，心衰竭出院後一年內又因感染再次入院者為感染組，無感染再入院者為對照組。我們使用傾向評分配對方法來平衡兩組之間的差異。在平均4.29±2.92年的追蹤時間中，感染組有86.19%的患者和對照組63.63%的患者發生MACE。多變項Cox比例風險分析顯示，感染組發生MACE的風險較高，包括全因死亡率、心肌梗塞、腦中風、心衰竭住院。總之，許多心衰竭患者出院後常發生急性感染需要重新入院。與沒有任何感染的患者相比，因感染再次入院後的患者心血管結果會變得更差。

Sung, P.-H., Yen, H.-K., Yang, S.-M., & Lu, K.-C. (2023). Nanomaterials, 13(7), 1197. Read this article

We report an efficient method to synthesize undoped and K-doped rare cubic tungsten trioxide nanowires through the thermal evaporation of WO3 powder without a catalyst. The WO3 nanowires are reproducible and stable with a low-cost growth process. The thermal evaporation processing was conducted in a three-zone horizontal tube furnace over a temperature range of 550–850 °C, where multiple substrates were placed at different temperature zones. The processing parameters, including pressure, temperature, type of gas, and flow rate, were varied and studied in terms of their influence on the morphology, aspect ratio and density of the nanowires. The morphologies of the products were observed with scanning electron microscopy. High resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies were conducted to further identify the chemical composition, crystal structure and growth direction of the nanostructures. Additionally, the growth mechanism has been proposed. Furthermore, we investigated the potassium doping effect on the physical properties of the nanostructures. Photoluminescence measurements show that there were shorter emission bands at 360 nm and 410 nm. Field emission measurements show that the doping effect significantly reduced the turn-on electric field and increased the enhancement factor. Furthermore, as compared with related previous research, the K-doped WO3 nanowires synthesized in this study exhibited excellent field emission properties, including a superior field enhancement factor and turn-on electric field. The study reveals the potential of WO3 nanowires in promising applications for sensors, field emitters and light-emitting diodes.

我們報導一種在不使用催化劑的情況下，透過熱蒸鍍法合成無摻雜及鉀摻雜的立方晶結構三氧化鎢奈米線的方法；此方法在三區水平爐管中進行，溫度範圍在550°C到850°C之間，基板與三氧化鎢粉末分別放置在不同的溫度區域。三氧化鎢奈米線具有可重複性、高穩定性及低製程成本等優勢。本實驗通過改變壓力、溫度、氣體種類和載流氣體等參數，研究不同參數對奈米線的形貌、長徑比及密度的影響。我們利用掃描式電子顯微鏡來觀察奈米線的形貌，再利用高解析穿透式電子顯微鏡、X光電子能譜儀和X光繞射儀進一步確定奈米結構的化學成分、晶體結構及生長方向。我們亦解釋了三氧化鎢奈米線的生長機制並深入探討鉀的摻雜對奈米結構物理性質的影響。螢光光譜儀的測量結果顯示360 nm 和 410 nm 處有較短的發射峰。場發射特性測量則顯示鉀的摻雜顯著降低啟動電場並提高場效增益因子，與之前的相關研究相比，本研究合成的鉀摻雜三氧化鎢奈米線展現出優異的場發射性質，包括優異的場效增益因子與啟動電場，亦揭示三氧化鎢奈米線在傳感器、場發射器及發光二極管領域之潛力。

Chen, C.-F., Fu, C., & Siao, P.-Y. (2023). Transportation Research Part D: Transport and Environment, 121, 103837. Read this article

Electric motor scooter (e-moped) sharing, an innovative shared mobility service, has recently attracted attention in urban transport systems. It is challenging to operate the service while Motorcycles and mopeds are prevalent. The study explores individual preferences toward the services using stated preference data collected in Taiwan. An integrated choice and latent variable approach is employed to investigate individuals' preferences related to e-moped sharing attributes and latent variables. The results show that service attributes such as base time, pay-per-minute fees, and the walking time to access an available vehicle decrease choice likelihood while returning to a vehicle without additional procedure, and e-mopeds with hedonic brands increase it. The impacts of those latent variables (advocacy for the service, hedonic motivation, and attitudes toward the service) varied in the groups with and without past riding experience, providing insights into the service adoption. I've talked about the relevant implications and provided it for future research.

Lin, Y.-J., Wang, L.-C., Tsai, H.-P., Chi, C.-Y., Chang, C.-P., Chen, S.-H., & Wang, S.-M. (2023). Virus Research, 336, 199203. Read this article

Neonatal infection with nonpolio enteroviruses (EVs) causes nonspecific febrile illnesses and even life-threatening multiorgan failure. Hepatitis, which often results in hepatic necrosis followed by disseminated intravascular coagulopathy, is one of the most severe and frequent fatal neonatal EV infection complications. Coxsackievirus B (CVB) 1–5 and many echoviruses have been most commonly identified. Neonatal EV infection treatment has usually involved initial supportive care. Studies for CVB and echovirus infection treatments were developed for more than thirty years. Intravenous immunoglobulin and pleconaril therapy was performed in some clinical trials. Additionally, other studies demonstrated antiviral and/or anti-inflammatory pathogenesis mechanisms of neonatal EV hepatitis in in vitro or in vivo models. These treatments represented promising options for the clinical practice of neonatal EV hepatitis. However, further investigation is needed to elucidate the whole therapeutic potential and safety problems.

新生兒感染非小兒麻痺症腸病毒，大都會引起輕症，如非專一性發熱，但也會導致危急生命的多重器官衰竭。肝炎是新生兒腸病毒感染後，最常發生與最嚴重的併發症之一，會造成肝臟壞死及後續的彌散性血管內凝集。克沙奇病毒B 1-5型和許多伊科病毒是最常被鑑定出的。新生兒腸病毒感染後，經常使用支持性治療為主，治療克沙奇病毒及伊科病毒的研究已經發展超過30年，靜脈免疫球蛋白注射和pleconaril已被使用於一些臨床試驗中，此外，其他研究也朝向在細胞或活體中，探討抗病毒及抗發炎對於新生兒腸病毒肝炎的機制，這些研究代表在臨床上針對新生兒腸病毒肝炎有力的正面選項，然而，需要更進一步研究，來闡明完整的治療潛力以及安全性問題。

Tang, W.-R., Wu, C.-H., Yang, T.-H., Yen, Y.-T., Hung, K.-S., Wang, C.-J., & Shan, Y.-S. (2023). Scientific Reports, 13(1), 5429. Read this article

High-grade liver laceration is a common injury with bleeding as the main cause of death. Timely resuscitation and hemostasis are keys to the successful management. The impact of in-hospital trauma system on the quality of resuscitation and management in patients with traumatic high-grade liver laceration, however, was rarely reported. We retrospectively reviewed the impact of team-based approach on the quality and outcomes of high-grade traumatic liver laceration in our hospital. Patients with traumatic liver laceration between 2002 and 2020 were enrolled in this retrospective study. Inverse probability of treatment weighting (IPTW)-adjusted analysis using the propensity score were performed. Outcomes before the trauma team establishment (PTTE) and after the trauma team establishment (TTE) were compared. A total of 270 patients with liver trauma were included. After IPTW adjustment, interval between emergency department arrival and managements was shortened in the TTE group with a median of 11 min (p < 0.001) and 28 min (p < 0.001) in blood test reports and duration to CT scan, respectively. Duration to hemostatic treatments in the TTE group was also shorter by a median of 94 min in patients receiving embolization (p = 0.012) and 50 min in those undergoing surgery (p = 0.021). The TTE group had longer ICU-free days to day 28 (0.0 vs. 19.0 days, p = 0.010). In our study, trauma team approach had a survival benefit for traumatic high-grade liver injury patients with 65% reduction of risk of death within 72 h (Odds ratio (OR) = 0.35, 95% CI = 0.14–0.86) and 55% reduction of risk of in-hospital mortality (OR = 0.45, 95% CI = 0.23–0.87). A team-based approach might contribute to the survival benefit in patients with traumatic high-grade liver laceration by facilitating patient transfer from outside the hospital, through the diagnostic examination, and to the definitive hemostatic procedures.

嚴重肝撕裂傷是一種常見的傷害，出血是主要致命原因。及時的復甦和止血是成功治療的關鍵。然而，少有文獻報導醫院內外傷體系對嚴重肝撕裂傷患者的復甦和治療品質的影響。我們回顧性檢視我們醫院採用以團隊為基礎的治療方式對治療品質和預後的影響。我們收納了2002年至2020年間患有肝撕裂傷的病患。使用反向處理機率權重（IPTW）進行調整分析。比較了創傷團隊成立之前（PTTE）和成立之後（TTE）的結果。總共有270名肝創傷患者參與了這項研究。在IPTW調整後，TTE組的急診到達和治療之間的間隔顯著縮短，血液檢測報告和CT掃描的時間中位數分別為11分鐘（p < 0.001）和28分鐘（p < 0.001），。在TTE組中，接受栓塞治療的患者的止血治療時間縮短了94分鐘（p = 0.012），接受手術治療的患者則縮短了50分鐘（p = 0.021）。TTE組的患者在28天內的無需重症監護室的天數更長（0.0 vs. 19.0天，p = 0.010）。72小時內死亡風險降低了65%（勝算比（OR）=0.35，95% CI = 0.14–0.86），住院死亡風險降低了55%（OR = 0.45，95% CI = 0.23–0.87）。以團隊為基礎的治療方式可以藉由加速病患有院外轉入、縮短診斷以及止血時間增加病患存活機會。

Lin, R.-C., Chao, Y.-Y., Su, M.-T., Tsai, H.-L., Tsai, P.-Y., & Wang, C.-Y. (2024). Cellular Signalling, 113, 110934. Read this article

Recurrent miscarriage is defined as more than three pregnancy failures occurring before 20 weeks of gestation. Poor differentiation of the endometrial stroma or defective trophoblast cell invasion at the maternal-fetal interface leads to recurrent miscarriages. Several miRNAs, including miR-20b-5p, are aberrantly regulated in recurrent miscarriages; however, the underlying molecular mechanisms remain unclear. Primary cilia are antenna-like organelles that coordinate signaling during development and differentiation. Defective primary cilia formation leads to complications, such as recurrent miscarriage or preeclampsia. Here, we demonstrated that miR-20b-5p inhibited trophoblast cell invasion by blocking primary cilia formation. Mechanistically, miR-20b-5p targeted and inhibited ATG16L1 and ATG7 expression, thereby blocking autophagy. Defective autophagy reduced primary cilia formation and stopped ERK activation, which is a crucial signaling pathway for trophoblast invasion. Aspirin is used to prevent recurrent miscarriages in clinical settings. Treatment with aspirin inhibited miR-20b-5p levels, thus restoring primary cilia formation and trophoblast invasion. Thus, our findings uncovered the molecular mechanism by which miR-20b-5p suppressed primary cilia formation and trophoblast invasion by reducing the expression of ATG16L1 and ATG7. Moreover, we found that the defective phenotypes could be rescued by aspirin in recurrent miscarriage.

復發性流產定義為妊娠 20 週前發生 3 次以上妊娠失敗。子宮內膜基質分化不良或母胎界面滋養層細胞侵襲缺陷會導致復發性流產 。多種 miRNA包括 miR-20b-5p在復發性流產中受到異常調節；然而，潛在的分子機制仍不清楚。初級纖毛是類似天線的胞器，在發育和分化過程中協調訊號傳遞。初級纖毛形成缺陷會導致許多婦科併發症，例如復發性流產或子癇前症。在這篇研究，我們證明 miR-20b-5p 透過阻斷初級纖毛形成來抑制滋養層細胞侵襲。從機制上來講，miR-20b-5p 抑制 ATG16L1 和 ATG7 的表達，從而阻斷自噬作用。ERK 活化是滋養層侵襲的重要訊號路徑，自噬作用的缺陷會減少初級纖毛的形成並停止 ERK 激活。阿斯匹靈在臨床上用於預防復發性流產。阿斯匹靈會抑制 miR-20b-5p 的表現，從而恢復初級纖毛形成和滋養層侵襲。因此，我們的研究結果顯示了miR-20b-5p透過降低ATG16L1和ATG7的表達來抑制初級纖毛形成和滋養層侵襲的分子機制。此外，我們發現阿斯匹靈可以緩解復發性流產的狀況。

Liu, K., Chen, C.-Y., Wang, L.-S., Jo, H., & Kung, C.-C. (2023). Frontiers in Neuroscience. Read this article

In 2011, Brants et al. trained eight subjects to become Greeble experts and found a neural inversion effect [i.e., the upright Greeble elicited a higher response in the fusiform face area (FFA) than when it was inverted]. These effects were also seen with faces before and after training. Brants et al. therefore, claimed that these results reflected that subjects' saw Greeble as faces throughout training. However, Brants et al.'s claim presents two issues. First, their behavioral results did not replicate Gauthier and Tarr's 1997 results. Second, the literature review and meta-analysis of NIE in FFA indicate that it is not a valid index of face processing. To further examine these questions, the present study compared two training paradigms documented by Gauthier and colleagues in 1997 and 1998, and compared their effects on the brain. Results: These results of our experiments confirm that the two research assumptions behind Brants’ claim were invalid, and therefore conclusions invalidated.

2011 年，Brants 等人。訓練八位受試成為”古力寶” Greeble 專家並發現神經倒立效應 [亦即，直立的古力寶激發臉孔反應區（FFA）的反應高於其倒立時]。在訓練前後的臉孔刺激也看到了這些效果。 Brants 等人因此聲稱，這些結果反映了受試者在整個訓練過程中皆將 Greeble 視為面孔。然而，Brants等人的主張有兩個問題。首先，他們的行為結果並沒有複製Gauthier and Tarr在1997年的結果。其次，對 FFA 中 NIE 的文獻回顧和元分析(meta-analysis)都表明它無法作為臉孔處理的有效指標。為了進一步檢驗這些問題，本研究比較了 Gauthier 及其同事在 1997 年和 1998 年記錄的兩種訓練範式，並比較了它們對大腦的影響。結果: 我們的實驗這些結果驗證了他們背後的兩個研究假設屬為無效，也因此Brants 等人的結論亦為錯誤。

Wang, C.-C., Lin, C.-H., Chou, H.-W., Wang, C.-T., Liang, Y.-C., Wu, H.-T., & Ou, H.-Y. (2023). Biomedicines, 11(7), 1936. Read this article

Hepassocin is a hepatokine exhibiting a hepatic protective effect. We found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin after treatment for hyperthyroidism in the human study. In the cell study, treatment of hepassocin recombinant protein in HepG2 cells decreased triiodothyronine (T3)-induced aminotransferases elevation. These results indicated that a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction.

肝細胞生成素(Hepassocin)是一種具肝臟保護性作用的肝臟因子。在人體研究中，我們發現治療甲狀腺亢進後丙氨酸氨基轉移酶與血清肝細胞生成素皆顯著減少。在細胞研究中，給予HepG2細胞肝細胞生成素重組蛋白處理，可降低三碘甲狀腺素所導致的轉移酶增加。這些結果顯示血清肝細胞生成素的代償性增加可能在甲狀腺亢進所導致的肝功能異常中具保護性作用。

Chou, D., & Chen, P.-Y. (2023). Chaos, Solitons & Fractals, 172, 113611. Read this article

Computer simulations and in silico models are currently the best tools for understanding complex biological processes. However, the complexity of biological tissues, with multiple cellular mechanisms in response to changing physical and chemical external stimuli, makes the corresponding mathematical models highly nonlinear with numerous parameters. These parameters are crucial to the models but are often fitted for specific conditions, making the conclusions drawn difficult to generalize. Moreover, some of these parameters will be hard to obtain through either clinical measurements or experiments. Hence, in this study, we introduced a perceptron-based method to determine unknown parameters of water transfer coefficients in the cerebral multi-compartmental poroelasticity model. Based on the nature and conditions of the available data, we designed a straightforward and functional model to solve a steady-state inverse problem. Moreover, we added an analytical solution to restrict the learning tendency of the model. It is to be noted that we only evaluated the unknown parameters without fitting the solution of PDEs. We believe that this study presents a functional perceptron-based approach for investigating and demonstrating unknown parameters using the cerebral multi-compartmental poroelasticity model. Besides, the algorithm was fully presented since we believed that our scheme has the ability to utilise in various field for those who need to estimate unknown parameters in PDEs. Furthermore, we tested the efficiency and effectiveness of the proposed method and demonstrated how the framework can help estimate the parameters rapidly. Finally, we discussed the unmet needs and forecasted future tasks of this framework.

基於感知器的多孔彈性動力學求解腦模型逆問題的學習方法
電腦模擬和電腦模型是目前理解複雜生物過程的最佳工具。 然而，生物組織的複雜性，以及對不斷變化的物理和化學外部刺激的多種細胞機制的響應，使得相應的數學模型具有高度非線性和眾多參數。 這些參數對模型至關重要，但通常適合特定條件，使得得出的結論難以概括。 此外，其中一些參數很難通過臨床測量或實驗獲得。 因此，在本研究中，我們引入了一種基於感知器的方法來確定大腦多室孔彈性動力學模型中的未知水傳輸係數。 根據可用數據的性質和條件，我們設計了一個簡單且實用的模型來解決穩態反問題。 此外，我們添加了解析解來限制模型的學習傾向。 值得注意的是，我們只評估了未知參數，而沒有擬合偏微分方程的解。 我們相信這項研究提出了一種基於功能感知器的方法，用於使用大腦多孔彈性動力學模型研究和演示未知參數。 此外，由於我們相信本團隊所提出的方法能夠在各個領域中，應用於那些需要估計偏微分方程中未知參數的需求，因此對該算法進行了全面介紹。 此外，我們測試了所提出方法的效率和有效性，並演示了該框架如何幫助快速估計參數。 最後，我們討論了該框架未滿足的需求並預測了未來的任務。

Kao, C.-Y., Zhang, Y.-Z., Bregente, C. J. B., Kuo, P.-Y., Chen, P. K., Chao, J.-Y., Duong, T. T. T., Wang, M.-C., Thuy, T. T. D., Hidrosollo, J. H., Tsai, P.-F., Li, Y.-C., & Lin, W.-H. (2023). Epidemiology & Infection, 151, e155, Article e155. Read this article

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.

近二十年來關於肺炎克雷伯氏菌表型和基因型特徵變化的縱向研究很少。我們的研究目的是確定1999年至2022年從菌血症或泌尿道感染(UTI)患者分離的肺炎克雷伯氏菌的抗菌敏感性和毒力因子。從菌血症和泌尿道感染(UTI) 患者中分別分離出總共699株和1,267株肺炎克雷伯氏菌，並測定了他們對二十種抗生素的敏感性；PCR用於鑑定莢膜血清型和毒力相關基因。我們發現K64 和K1血清型分別在泌尿道感染和菌血症中最常見，近年來觀察到的K20、K47 和K64的頻率則逐漸增加。entB和wabG在所有分離株和血清型中占主導地位；最不常見的毒力基因是htrA。大多數分離株對碳青黴烯類、阿米卡星、替加環素和粘菌素敏感，但K20、K47和K64則除外，其抗藥性相對地廣泛。在 K1菌株中觀察到毒力基因的平均數量最高，其次是K2、K20和K5分離株，這表明它們對 K1的高毒性做出了貢獻。總結來說，我們發現二十年來肺炎克雷伯氏菌的抗菌敏感性、毒力基因譜和莢膜類型的分佈與其臨床來源相關。

Tung, C.-H., Wu, J.-E., Huang, M.-F., Wang, W.-L., Wu, Y.-Y., Tsai, Y.-T., Hsu, X.-R., Lin, S.-H., Chen, Y.-L., & Hong, T.-M. (2023). Cancer Cell International, 23(1), 207. Read this article

Lung cancer has the highest mortality rate in the world, and mounting evidence suggests that cancer stem cells (CSCs) are associated with poor prognosis, recurrence, and metastasis of lung cancer. It is urgent to identify new biomarkers and therapeutic targets for targeting lung CSCs. In this study, we demonstrated that USP5 expression were positively correlated with the stemness-associated signatures and poor outcomes in lung cancer specimens. We found that USP5 interacted with β-catenin, which resulted in deubiquitination, stabilization of β-catenin, and activation of Wnt/β-catenin pathway. Targeting USP5 with the small molecule WP1130 promoted the degradation of β-catenin, and showed great inhibitory effects on sphere formation, migration, and invasion. Finally, we identified a poor-prognosis subset of tumors characterized by high levels of USP5, Wnt signaling score, and Stemness score in two datasets. These findings reveal the clinical evidence for USP5-enhanced Wnt/β-catenin signaling in promoting lung cancer stemness and metastasis, implying that targeting USP5 could provide beneficial effects to improve lung cancer therapeutics.

泛素特異性肽酶5(USP5)透過去泛素化β-catenin而促進肺癌幹細胞特性
肺癌是目前死亡率最高的惡性腫瘤，諸多證據顯示癌症幹細胞（CSC）與肺癌的預後不良、復發和轉移有關。因此找到肺癌CSC的新生物標誌物和治療靶標至關重要。在本研究中，我們證明USP5的表達量與肺癌CSC相關特徵及病人較差的預後呈正相關。我們發現USP5透過與β-catenin相互作用而導致β-catenin的去泛素化，從而穩定Wnt/β-catenin途徑的激活。我們也利用靶向USP5的小分子藥物WP1130去促進β-catenin的降解，而達到抑制肺癌CSC特徵和癌轉移。臨床數據分析也顯示合併USP5表達量/Wnt信號得分/和Stemness評分可作為肺癌CSC的新生物標誌物。這些發現揭示了USP5增強Wnt/β-catenin信號傳導在促進肺癌幹性和轉移中的臨床證據，更表明靶向USP5可以為改善肺癌治療劑提供有益的效果。

Kuo, Y.-H., & Chen, H.-B. (2023). Physical Review Research, 5(4), 043139. Read this article

Along with the rapid development of quantum technologies, quantum computing has become a reality. Among the various applications of quantum computation, quantum simulation is arguably the most prominent one to demonstrate the quantum advantage of near-term quantum computing platforms. However, due to the limitations imposed by the significant noises and the topological qubit connectivity, simulating large-scale materials on near-term quantum computing platforms remains a troublesome problem. In this work, we propose an alternative approach to circumvent these difficulties. Our approach adaptively partitions the effects of a huge environment into small groups fitting into the limited performance of near-term quantum computing platforms. Then each small group can be implemented independently. Finally, the outputs of all small groups are combined together to recover the effects of the huge environment. We have explicitly demonstrated our approach on IBMQ by simulating the free induction decay (FID) of the electron spin in diamond NV center. Additionally, our approach can also realize the manipulation of the nonclassicality of the FID dynamics by simulating the external magnetic field and the dynamical nuclear spin polarization. In conclusion, we have established a flexible approach capable of simulating large-scale materials by adaptively distributing the computing loading to different devices and circumventing the limitations of near-term quantum computers.

隨著量子技術的快速發展，量子運算已經成為現實。在量子運算的各種應用中，量子模擬可以說是展示近期量子運算平台的量子優勢的最顯著的應用。然而，礙於明顯的雜訊和量子位元的拓樸連接性所帶來的限制，在近期量子運算平台上模擬大規模材料仍然是一個棘手的問題。在本工作中，我們設計了一種替代方法來規避這些困難。我們的方法自適應地將巨大環境的效應分割為適合近期量子計算平台有限性能的小群組，然後每個小群組就可以獨立地被模擬。 最後將所有小群組的輸出組合在一起，便可得到環境的效應。為了清楚地展示我們的方法，我們在IBMQ量子電腦上模擬鑽石氮空缺中心電子自旋的自由感應衰退(FID)。此外，我們的方法也成功的模擬了外加磁場與動態核自旋極化對於電子FID過程中之非古典性的效應。總結來說，我們建立了一種靈活的方法，能夠透過自適應地將計算負載分配到不同的設備，藉此來規避近期量子電腦的性能限制，並可模擬大型材料。

Wu, Y.-L., Wang, C.-S., Weng, W.-C., & Lin, Y.-C. (2023). Sensors, 23(18), 7733. Read this article

URS-10 serve as a rapid test capable of detecting 10 distinct parameters in urine samples. Although the operational procedure is straightforward, the variegated color changes exhibited in the outcomes of individual parameters render it challenging for lay users to deduce the results. In this study, we successfully developed a cloud-based health checkup system that can be used in an indoor environment. The system is used by placing a URS-10 test strip on a colorimetric board developed for this study, then using a smartphone application to take images which are uploaded to a server for cloud computing. Finally, the interpretation results are stored in the cloud and sent back to the smartphone to be checked by the user. This study uses color correction technology to reduce the impact of chromatic aberration and enable correct interpretation of results.

URS-10為一種快篩試劑，能夠檢測尿液中10種不同品項，儘管操作過程很簡單，但各個品項檢測結果的顏色變化一般使用者難以辨別。在這項研究中，我們成功開發了一種建立於室內使用的雲端健康檢查系統。該系統的使用方法是將URS-10測試條放置在本研究開發的比色板上，使用本研究開發的手機應用程式拍攝影像，並將影像上傳到雲端伺服器進行判讀。最後，判讀結果儲存在雲端並發送回智慧型手機供用戶檢查。本研究採用色彩校正的技術可以減少色差影響，使其能正確判讀結果。

Chang, L.-C., Chin, Y.-C., Wu, P.-C., Wei, Y.-F., Wu, H.-C., Cheng, T.-Y., Liu, Y.-F., Huang, C.-C., & Su, W.-P. (2024). Nano Today, 54, 23(18), 102070. Read this article

The tumor microenvironment (TME), where immunosuppressive cells such as tumor-associated macrophages (TAMs) proliferate, is the main cause of resistance to antineoplastic treatment for KRAS-driven lung cancer. In this study, we synthesized polymer-based nanoparticles composed of a 16 nm-sized Au core and the amphiphile, poly-(styrene-alt-maleic acid) (PSMA), via a hydrothermal procedure for carrying the multi-receptor tyrosine kinase inhibitor, sitravatinib (Sit), in a new nanodrug (Au@PSMA-Sit). Au@PSMA-Sit was water soluble and showed high sitravatinib loading and good stability under numerous solution conditions, and was degraded by intracellular esterase to release sitravatinib. In Lewis lung carcinoma (LLC) orthotopic tumor mice, Au@PSMA-Sit enhanced antitumor efficiency by remodeling the TME. Immune profiling with single-cell RNA sequencing showed that Au@PSMA-Sit treatment increased the CD8 T cell cluster and decreased the M2-type macrophage cluster compared to treatment with pure sitravatinib. Au@PSMA-Sit reduced LLC cell proliferation and upgraded M1 polarization of LLC-cocultured TAMs through inhibition of TAM receptors (Tyro3, AXL, and MerTK) after intracellular release of sitravatinib. Au@PSMA-Sit promoted endocytosis-induced endoplasmic reticulum (ER) stress-mediated spleen tyrosine kinase signaling activation, which regulated immunosuppressive TAMs metabolism via enhancement of mitochondrial fission and glycolysis leading to immunogenic modulation. Furthermore, Au@PSMA-Sit enhanced immunogenic cell death through endocytosis/ER stress-mediated release of CRT and HMGB1 from LLC cells, leading to dendritic cell maturation and cytotoxic T cell activation. Therefore, macrophage and CD8 T cell depletion using blocking antibodies diminished the antitumor efficiency of Au@PSMA-Sit. Our results indicate the potential of nano-formulated sitravatinib for strengthening anti-cancer effects in the absence of immunotherapy via immunogenic remodeling of the KRAS-mutant lung TME.

腫瘤微環境 (TME) 是腫瘤相關巨噬細胞 (TAM) 等免疫抑制細胞增殖的場所，是 KRAS-driven之肺癌抗腫瘤治療失敗的主要原因。在這項研究中，我們透過水熱法合成了由16 nm大小的Au 核和PSMA組成的聚合物奈米顆粒，用於攜帶multi-tyrosine kinase inhibitor-sitravatinib (Sit)，一種新型奈米藥物 (Au@PSMA-Sit)。 Au@PSMA-Sit 是水溶性的，在多種溶液條件下表現出高sitravatinib載量和良好的穩定性，並被細胞內esterase降解以釋放sitravatinib。在 Lewis 肺癌 (LLC) KRASG12C 突變原位腫瘤小鼠中，Au@PSMA-Sit 透過重塑 TME 提高了抗腫瘤效率。單細胞 RNA 定序免疫分析表明，與純 Sitravatinib 治療相比，Au@PSMA-Sit 治療增加了CD8 T細胞cluster並減少了 M2 型巨噬細胞cluster。 Au@PSMA-Sit 透過在細胞內釋放 Sitravatinib 後抑制 TAM 受體（分別是Tyro3、AXL 和 MerTK）來減少 LLC 細胞增殖，並在與LLC 共培養TAM時，增強的M1 極化。 Au@PSMA-Sit 可促進endocytosis所誘導的內質網(ER) 壓力所產生SYK kinase活化，同時也增強mitochondrial fission 及glycolysis 產生M1極化。此外在LLC 細胞，Au@PSMA-Sit 透過endocytosis所誘導的內質網(ER) 壓力，進而釋放 CRT 和 HMGB1 到TME中，導致樹突細胞的成熟和CD8 T 細胞活化，進而增強immunogenic cell death。反之，使用macrophage and CD8 T cell depletion的治療則會降低 Au@PSMA-Sit 的抗腫瘤效率。我們的結果表明在KRAS 突變LLC肺癌中，在未使用免疫治療的情況下，奈米製劑Sitravatinib，會透過重塑肺部的TME，具有增強抗癌作用的潛力。

Chen, Y.-Y., Tzeng, S.-Y., Yen, Y.-Y., Cheng, N.-Y., & Tseng, S.-H. (2023). NScientific Reports, 13(1), 23(18), 20149. Read this article

Maintaining adequate skin hydration is vital for healthy skin function. This study investigated using diffuse reflectance spectroscopy (DRS) to noninvasively assess changes in skin optical properties related to variations in hydration state. DRS allows quantitative measurement of absorption and scattering properties in superficial skin layers. Ten healthy subjects underwent facial mask or soaked cotton pad treatment for 20 minutes to induce skin hydration changes. The DRS-derived absorption coefficient at 980nm, a characteristic wavelength for water, showed high correlation (r=0.93 for facial mask and 0.82 for cotton pad) with skin capacitance indicating hydration level. Participants reporting skin tightness sensation (Group A) exhibited decreased reduced scattering coefficient after treatments, suggesting DRS scattering profiles can detect cellular swelling. Overall, DRS sensitively monitored skin optical property changes reflecting dynamic hydration variation from different treatments. This could offer a convenient approach for quantitative evaluation of treatment efficacy and subjective sensations.

維持適當的皮膚水合是健康皮膚功能的關鍵。本研究探討應用漫反射光譜儀非侵入性定量評估與水合變化相關的皮膚吸收與散射特性。該技術可測量表淺皮膚層的光學特性。10名健康受試者接受20分鐘面膜或浸濕棉片處理,誘發皮膚水合變化。結果顯示,代表水分吸收的980奈米處吸收係數,與表示水合度的皮膚電容量間存在高相關度(r值在面膜組0.93、棉片組0.82)。感受皮膚緊繃的A組受試者,治療後顯示散射係數下降,表示細胞腫脹的偵測。綜上所述, 本技術可敏感監測不同治療導致皮膚光學特性動態變化,反映水合變化。未來可作為量化評估治療效果及主觀感受性的工具。

Chou, W.-C., Chou, Y.-Y., Pan, Y.-W., Ou, T.-Y., & Tsai, M.-C. (2023). Journal of Eating Disorders, 11(1), 23(18), 158. Read this article

Adolescents and young adults (AYAs) with diabetes mellitus (DM) are prone to eating disorders that may worsen metabolic control. In this study, we enrolled 110 patients with DM aged 10-30 years receiving insulin treatment from 2019 to 2021. After obtaining informed consent, we assessed various HbA1c measures indicating glycemic control, DE/IR behavior using the modified SCOFF questionnaire, weight-control practices, and anxious and depressive symptoms using the Hospital Anxiety and Depression Scale. Results found 17.6% restricting insulin use and 6.3% self-medicating for weight control (higher in type 2 DM than type 1 DM). Hierarchical regression analyses showed HbA1c standard deviation, body image, and dieting associated with disordered eating and insulin restriction (DE/IR) behavior that was further associated with anxiety and depression. DE/IR behavior is not uncommon among AYAs with DM, and its clinical implications need further exploration.

患有糖尿病年輕人容易出現飲食失調，可能惡化代謝控制。於本研究調查中，我們招募了110名在2019 年至2021年間接受胰島素治療的10-30 歲糖尿病患者。在獲得知情同意後，我們使用改良的SCOFF 評估了各種糖化血色素指標，顯示血糖控制、飲食失調和胰島素限制行為問卷、體重控制措施，以及使用醫院焦慮和憂鬱量表的焦慮和憂鬱症狀。我結果發現 17.6% 的患者限制胰島素使用，6.3% 的患者透過自我藥物控制控制體重（第2型糖尿病患者的比例高於第1型糖尿病患者）。分層迴歸分析顯示糖化血色素標準差、身體形象、和節食，與飲食失調和胰島素限制行為。此行為進一步與焦慮和憂鬱相關。總結糖尿病的年輕人中飲食失調和胰島素限制行為不少見，其臨床意義需要進一步探討。

Achmad, B. F., Fitriawan, A. S., Kurniawan, D., & Chen, H.-M. (2023). Heliyon, 9(11). Read this article

This study aimed to examine the determinants of depression symptoms and the mediating effect of self-esteem on the relationship between academic self-efficacy and depression symptoms among nursing students who participate in blended learning. A cross-sectional study design using a convenience sampling method was employed, and 534 nursing students were recruited from ten universities across five provinces and two major Indonesian islands. Instruments included the General Self-Efficacy Scale, Rosenberg Self-Esteem Scale, and a 9-item Patient Health Questionnaire. Data were analyzed by hierarchical linear regression and mediation effect analysis using SPSS PROCESS macro version 4.1. The results showed that of the 534 participants, 213 (39.14 %) experienced moderate-to-severe depression symptoms. The hierarchical linear regression analysis found that online learning difficulties and self-esteem were two significant determinants of depression symptoms. The medication effect analysis suggested that self-esteem mediated the relationship between academic self-efficacy and depression symptoms. The study concluded the importance of understanding the online learning difficulties experienced by blended learning students and improving their self-esteem by maximizing academic self-efficacy to prevent depression symptoms.
Keywords: Academic self-efficacy, blended learning, depression symptoms, self-esteem

混合式學習護生之自尊對學業自我效能與憂鬱症狀間的中介效果
本研究目的旨在探討參與混合式學習的護生之憂鬱症狀的決定因素，以及自尊在學業自我效能與憂鬱症狀關係中的中介效果。採橫斷式研究設計，以便利取樣法共招募來自印尼二大島嶼、五個省份、10所大學共534位護生加入研究。研究工具包含一般自我效能量表、自信心量表和病人健康問卷-9等。資料分析則使用 SPSS PROCESS macro版本 4.0進行階層線性迴歸與中介效果分析。研究結果顯示，在534位的護生中，有216位(39.14%)有中度至重度的憂鬱症狀。線上學習障礙及自尊是發生憂鬱症狀的二大關鍵性因素。中介效果分析則發現，自尊中介學業自我效能感與憂鬱症狀之間的關係。本究結果結論在了解混合式學習學生線上學習障礙的重要性，透過盡可能地提高其學業自我效能以期改善自尊，進而預防憂鬱症狀的發生。
關鍵字：學業自我效能、混合式學習、憂鬱症狀、自尊

Chang, Y.-H., Hsing, C.-H., Chiu, C.-J., Wu, Y.-R., Hsu, S.-M., & Hsu, Y.-H. (2023). Journal of Neuroinflammation, 20(1), 279. Read this article

In patients with wet/exudative age-related macular degeneration (AMD), vision loss is often linked to choroidal neovascularization (CNV). As the primary cause of irreversible vision impairment in older adults, AMD poses a significant health concern. Interleukin-17A (IL-17A), a component associated with autoimmune diseases, has been found in elevated levels in the serum of wet AMD patients. However, the impact of IL-17A on AMD progression remains unclear. This study investigates IL-17A's role using a laser-induced CNV mouse model. Results show that IL-17A deficiency leads to larger CNV lesions, decreased immune cell populations, and altered cytokine levels in mice. IL-17A-producing γδ T cells play a time-dependent role in response to laser injury. Additionally, in vitro experiments demonstrate IL-17A's protective effects, suggesting a novel regulatory role in wet AMD's ocular microenvironment. Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

患有濕性/滲出性老年性黃斑部病變（AMD）的患者，視力損失通常與脈絡膜新生血管（CNV）有關。作為老年人不可逆視力損傷的主要原因，AMD是一個重大的健康問題。發現患有濕性AMD的患者血清中IL-17A水平升高，而IL-17A是與某些自體免疫疾病相關的成分。然而，IL-17A對AMD進展的影響仍不清楚。這項研究利用雷射激光誘導的CNV小鼠模型來探討IL-17A的作用。結果顯示，IL-17A缺乏小鼠中導致較大的CNV病灶，減少了小鼠眼中的免疫細胞群，並改變了細胞激素的水平。在野生型小鼠中，IL-17A產生的γδ T細胞數量在雷射激光損傷後的7至28天間呈時間依賴性增加。此外，在體外實驗中顯示，IL-17A對於氧化壓力誘導條件下的ARPE-19人類視網膜色素上皮細胞有保護作用。我們的研究結果為雷射激光誘導的CNV模型中IL-17A的保護效應提供了新的見解，同時發現在濕性AMD中，IL-17A生成的γδT細胞在眼部微環境中發揮的新穎的調控作用。

Huang, W.-C., Yang, A. S.-H., Tsai, D. H.-T., Shao, S.-C., Lin, S.-J., & Lai, E. C.-C. (2023). BMJ, 382, e076045. Read this article

Anticholinergic burden refers to the cumulative effect of using multiple medications with anticholinergic properties concomitantly. Previous studies have reported an association between anticholinergic burden and increased cardiovascular risk, but they did not consider the potential issue of protopathic bias. In this nationwide study, we implemented the case-case-time control analyses, which consisted of two case-crossover analysis—a case crossover analysis and a control crossover analysis consisting of future cases to eliminate the time invariant confounders and protopathic bias. We found recently raised anticholinergic burden was associated with an increased risk of acute cardiovascular events. Although the results were substantially diminished after considering the effects of protopathic bias through the case-case-time-control design, the bias did not fully explain away the increased risk. Moreover, the association was further strengthened by the evidence of a dose-response relationship between anticholinergic burden and the risk of acute cardiovascular events. Given that many drugs have anticholinergic effects in addition to their primary mechanism of action, healthcare providers should increase their awareness of these effects and consider reducing unnecessary drug use

抗膽鹼負荷指的是患者使用具有抗膽鹼活性的藥物所產生之累加性影響。先前研究中指出，抗膽鹼負荷可能會增加心血管事件之發生，然而，其並未考慮潛在之倒果為因偏差。本研究為全國性研究，我們透過病例–病例–時間控制分析，即透過病例交叉研究以及未來病例之控制交叉研究來進行分析，以自我對照之設計來消除時間恆定性之干擾因子。我們發現患者短期增加抗膽鹼負荷會增加急性心血管事件之發生；儘管該風險在透過病例–病例–時間控制分析處理後顯著降低，該偏差仍無法完全解釋增加之風險。此外，我們進一步透過劑量–反應相關性加強我們觀察到的相關性。鑑於許多藥物的抗膽鹼作用並非其主要作用，臨床照護者在使用相關藥物時應提高驚覺，並考慮減少不必要的藥物使用。