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.
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/).
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）
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
18. Highly Transparent and Polarization-Maintained Terahertz Plasmonic Metamaterials Based on Metal-Wire-Woven Hole Arrays: Fundamentals and Characterization of Transmission Spectral Peaks.
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.
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.
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.
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.
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.
22. Investigating the clinical implication of corneometer and mexameter readings towards objective, efficient evaluation of psoriasis vulgaris severity.
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
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.
25. Relationship Between Weight Status and Self-Image Mediated by Pubertal Timing and Athletic Competence: A Cohort Study With Taiwanese Adolescents
Kuo, J.-H., Ubeda Herrera, J. J., Liu, C.-Y., Lee, T.-H., Strong, C., Lin, C.-Y., Chang, Y.-H., Lin, Y.-C., Hsieh, Y.-P., & Tsai, M.-C. (2022). [Original Research]. Frontiers in Public Health, 10. Read this article
Self-image reflects overall self-acceptance in developing adolescents. Using a representative cohort of Taiwanese youth, this study aims to explore the relationship between weight status, pubertal timing, athletic competence, and adolescent self-image. Data come from the Taiwan Youth Project that comprised a longitudinal cohort of adolescents (N = 2690, 51% males, Mage = 13.3 ± 0.5 years) surveyed annually from seventh grade. Self-image was measured by perceived satisfaction with appearance and physique. Pubertal timing was defined using the Pubertal Developmental Scale. Athletic competence was assessed by experiences with participation in competitive sports and self-perceived talent for sports. In order to test for mediating roles of pubertal timing and athletic competence, Hayes' PROCESS macro on SPSS was conducted. The boot-strapped 95% confidence intervals indicated significant mediating effects of pubertal timing (β = −0.008, [−0.015, −0.001]) and athletic competence (β = −0.006, [−0.011, −0.002]) in the link between BMI and self–image in females. Moreover, BMI at baseline were associated with long-term self-image in males (β = −0.037, [−0.057, −0.017]) and females (β = 0.132, [0.073, 0.190]). Understanding the mediating factors may help enhance adolescents' self-image by providing guidance on healthy weight and physical activity behaviors according to different stages of pubertal progression.
26. Vaccine nationalism among the public: A cross-country experimental evidence of own-country bias towards COVID-19 vaccination.
Barceló, J., Sheen, G. C.-H., Tung, H. H., & Wu, W.-C. (2022). Social Science & Medicine, 310, 115278. Read this article
In “Vaccine Nationalism Among the Public: Cross-country Experimental Evidence of Own-country Bias Towards COVID-19 Vac- cination” (joint with Joan Barceló, Hans H. Tung, and Wen-Chin Wu; published in Social Science & Medicine), we administered an experiment requesting 15,000 adult citizens across 14 individual countries from around the world to assess 450,000 profiles of vaccines that randomly varied across seven attributes. We showed that, beyond vaccine fundamentals such as efficacy rate and duration of the protection, citizens systematically favored vaccines developed and produced in their own country of residence. The extent of preference in favor of vaccines developed and produced within the national borders is particularly large among citizens who identify more strongly with their nation, suggesting nationalism plays a role in explaining the bias in favor of vaccines developed and produced locally. This public opinion bias on vaccine preferences has significant theoretical and practical implications.
在 “Vaccine Nationalism Among the Public: A Cross-country Experi- mental Evidence of Own-country Bias towards COVID-19 Vaccination”這篇文章中，我們使用聯合分析法(conjoint analysis)進行了一個包含台灣日韓美中英法等、橫跨十四個國家的大規模問卷實驗，我們的實驗結果發現，民眾在進行疫苗選擇時，除了疫苗的保護力、保護力持續期間長短等疫苗的基本特質外，在控制其他條件下，民眾還會特別偏好自己國家所研發的疫苗。
27. Combination of Plasmon-Mediated Photochemistry and Seed-Mediated Methods for Synthesis of Bicomponent Nanocrystals.
Here, we fabricate heterogeneous nanocrystals by integrating seed-mediated and plasmon-mediated photochemistry. Using metal nanocrystals as seed crystals, bimetallic nanocrystals can be generated by depositing or reducing guest metal nanocrystals on the host seed crystals, and semiconductor-metal nanocrystals can be generated by sulfidation on the surface of metal nanocrystals. Since plasmonic nanocrystals act as seeds for bicomponent nanocrystal synthesis, plasmonic-induced "hot electrons" around the seeds can be used to accelerate the formation rate of bicomponent nanocrystals, leading to changes in nanocrystal morphology. This new synthetic method should enable the fabrication of a variety of multicomponent nanocrystals with desirable functionalities for potential applications such as photocatalysts, chemical/biosensors, and biomedicine.
In intensive care units, after endotracheal intubation, the position of the endotracheal tube (ETT) should be checked to avoid complications. The malposition can be detected by the distance between the ETT tip and the Carina (ETT–Carina distance). However, it struggles with a limited performance for two major problems, i.e., occlusion by external machine and poor chest radiograph quality. While previous studies addressed these problems, they always suffered from manual intervention requirements. Therefore, this paper aimed to locate the ETT tip and the Carina more accurately for detecting the malposition without manual intervention. The proposed architecture was composed of “Fully Convolutional One-Stage Object Detection”, a Coarse-to-Fine Attention module, and a segmentation branch. Moreover, a post-process algorithm was adopted to refine the detection results. With the dataset provided by National Cheng Kung University Hospital, the accuracy of detecting the malposition achieved 88.82%, and the ETT–Carina distance errors were less than 5.333 ± 6.240 mm.
29. Iterative Hard-Decision Decoding Algorithms for Binary Reed-Muller Codes.
Ni, Y. T., Nguyen, D. N., Liao, F. K., Kao, T. C., & Chen, C. Y. (2022). IEEE Access, 10, 59373-59382. Read this article
In this paper, novel hard-decision iterative decoding algorithms for binary Reed-Muller (RM) codes are presented. First, two algorithms are devised based on the majority-logic decoding algorithm with reliability measures of the received sequence. The bit-flipping (BF) and the normalized bit-flipping (NBF) decoding algorithms are hard-decision decoding algorithms. According to the updated hard reliability measures, the BF and NBF algorithms flip one bit of the received hard-decision sequence at a time in each iteration. The NBF decoding algorithm performs better than the BF decoding algorithm by normalizing the reliability measures of the information bits. Moreover, the BF and NBF algorithms are modified to flip multiple bits in one iteration to reduce the average number of iterations. The modified decoding algorithms are called the multiple-bits-flipping (MBF) algorithm and the normalized multiple-bits-flipping (NMBF) algorithm, respectively. The proposed algorithms have low computational complexities and can converge rapidly after a small number of iterations.
Schizophrenia (SZ) is influenced by genetic and environmental factors, and associated with chronic neuroinflammation. If the symptoms express after adolescence, environmental impacts are more substantial, and the disease is defined as adult-onset schizophrenia (AOS). Effects of environmental factors on antibody responses such as Escherichia coli (E. coli) to immunoglobulin G (IgG) and immunoglobulin M (IgM) might increase the severity of symptoms in SZ via the gut-brain axis. The purpose of this study is to reveal antibody profiles of SZ against bacterial protein antigens. We analyzed the IgG and IgM antibodies using E. coli proteome microarrays from 80 SZ patients and 40 healthy controls (HC). We identified the protein yjjU, livG and ftsE can form the best combination panel to classify IgG in AOS vs HC with accuracy of 0.8. Also, these antigens are enriched in ABC transporter related domains, including human ABCB1 protein. The findings suggest that AOS had different immunoglobulin production compared to early-onset schizophrenia (EOS) and HC.
Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive. Here, we show that glycoprotein E (gE) binds to the cellular protein, annexin A1 (Anx-A1) to enhance infection. Anx-A1 can be detected on the surface of cells permissive for HSV-1 before infection and on virions. Suppression of Anx-A1 or its receptor, formyl peptide receptor 2 (FPR2), on the cell surface and gE or Anx-A1 on HSV-1 envelopes reduced virus binding to cells. Importantly, Anx-A1 knockout, Anx-A1 knockdown, or treatments with the FPR2 antagonist reduced the mortality and tissue viral loads of infected mice. Our results show that Anx-A1 is a novel enhancing factor of HSV-1 infection. Anx-A1-deficient mice displayed no evident physiology and behavior changes. Hence, targeting Anx-A1 and FPR2 could be a promising prophylaxis or adjuvant therapy to decrease HSV-1 lethality.
Osteoporotic vertebral fracture is so called “silent fracture”. Two-third of vertebral fractures are under-diagnosed due to no obvious symptom in clinical practice. As previous studies, numerous approved agents are available to treat osteoporosis effectively. However, a treatment gap exists due to under diagnosis and low treatment rate. There were few studies focused on factors associated with outpatient visits and osteoporosis treatment after vertebral fracture. We would evaluate the factors associated with outpatient visits after vertebral fracture from subjects of Tianliao study between 2009 and 2010. Furthermore, information about outpatient visits and osteoporosis medication prescriptions were derived from National Health Insurance Research database.
Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.
Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fc-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection.
35. A universal strategy for the fabrication of single-photon and multiphoton NIR nanoparticles by loading organic dyes into water-soluble polymer nanosponges.
The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes into water-soluble polymer nanosponges composed of poly(styrene-altmaleic acid) (PSMA). This packaging strategy includes commercial dyes and our newly synthesized organic dyes (> 85% loading) designed for OPVs, DSSCs, and OLEDs applications preventing their spontaneous aggregation in aqueous solutions and improving their biocompatibility. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to NIR emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were also performed photodynamic therapy for the photolysis of cancer cells under 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.
To determine whether body composition indices interact with age and gender as a predictor of all-cause mortality, 1,200 participants at least 40 years of age were recruited in 2009 and 2010. A multi-frequency bioelectrical impedance analysis device was used to measure each participant’s body composition indices, including the fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass index (SMMI), and visceral fat area index (VFAI). A baseline questionnaire was used to collect demographic information about lifestyle habits, socioeconomic status, and medical conditions. All claimed records of death from 2009 to 2018 in the National Health Insurance Research Databank were identified. The all-cause mortality rate was 8.67% after a mean follow-up period of 5.86±2.39 person-years. The Cox proportional hazard model analysis showed significantly negative associations between FFMI or SMMI with all-cause mortality in the total group and those aged > = 65 y/o. The FFMI and SMMI were negative predictors of mortality in both genders. The FMI and VFAI were positive predictors of mortality exclusively in females. In conclusion, the SMMI is a better predictor of mortality than the BMI, FMI, and FFMI, especially in older adults. A higher fat mass or visceral fat distribution may predict higher mortality in females.
本研究目的在瞭解身體組成指標如何在與年齡與性別的互動下成為全死因死亡率的關係。於2009年到2010年間，共收錄四十歲以上1200位受試者參與研究。使用多頻率生物電阻分析儀測量每位受試者的身體組成指標，包括脂肪量指標(fat mass index, FMI)、除脂肪量指標(fat free mass index, FFMI)、骨骼肌肉量指標(skeletal muscle mass index, SMMI)以及內臟脂肪區域指標(visceral fat area index, VFAI)。使用基礎問卷收集受試者的基本地域資料包含生活習慣、社經地位以及身體健康狀況等。所有死亡發生記錄的資料來自2009年到2018年間國家健康保險研究資料庫。研究結果發現，經過平均5.86±2.39人年的追蹤後，受試者的全死因死亡率為8.67%。利用Cox proportional hazard model分析發現在所有受試者以及大於65歲以上族群，FFMI或SMMI與全死因脂肪率呈現有意義的負相關性。男女性受試者FFMI 以及SMMI 皆為死亡的負向預測因子，FMI 與VFAI 則僅在女性族群為正向的死亡預測因子。總結來說，相較於BMI、FMI 以及FFMI 而言，SMMI是最佳的死亡預測因子，此現象在老年族群更為明顯。女性有較高的脂肪量或內臟脂肪分布則可能有較高的死亡率。
37. Synthesis and Characterization of Indium Tin Oxide Nanowires with Surface Modification of Silver Nanoparticles by Electrochemical Method.
In this study, indium tin oxide nanowires (ITO NWs) with high density and crystallinity were synthesized by chemical vapor deposition (CVD) method via vapor-liquid-solid (VLS) route; the NWs were decorated with silver on the surface by an electrochemical method. The ITO NWs possessed great morphologies with length of 5~10 μm and an average diameter of 58.1 nm. The room temperature photoluminescence (PL) studies show that the ITO NWs were of visible light-emitting properties, and there were a large number of oxygen vacancies on the surface. The successful modification of Ag was confirmed by TEM, XRD and XPS. PL analysis reveals that there was an extra Ag signal at around 1.895 eV, indicating the potential application of Ag-ITO NWs as na-noscale optical materials. Electrical measurements show that more Ag-nanoparticles on the surface of ITO NWs contributed to higher resistivity, demonstrating the change of the electron transmission channel of the Ag-ITO NWs. ITO NWs and Ag-ITO NWs are expected to enhance the performance of electronic and optoelectronics devices.
38. A New Instrument Combines Cognitive and Social Functioning Items for Detecting Mild Cognitive Impairment and Dementia in Parkinson’s Disease.
Yu, Y.-W., Tan, C.-H., Su, H.-C., Chien, C.-Y., Sung, P.-S., Lin, T.-Y., Lee, T.-L., & Yu, R.-L. (2022). Frontiers in Aging Neuroscience, 14. Read this article
Mini-mental status examination (MMSE) and Montreal Cognitive Assessment (MoCA) are commonly used clinical tools to screen for cognitive impairment in patients with Parkinson's disease (PD). We developed the Parkinson's Disease Social Functioning Scale (PDSFS) and demonstrated good psychometric properties for assessing social functioning in patients with PD. This study validates and simplifies commonly used clinical assessment tools and develops a comprehensive test of cognitive and social functioning to aid in detecting PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD). We found that the cut-off score of the short MMSE to detect PD-MCI is 26 points, while the cut-off scores of the MoCA to detect PD-MCI and PDD are 23 and 18, respectively. The short version of the MoCA includes three sub-tests: visuospatial/executive, memory subtest, and orientation sense, with a total score of 16 points. The cut-off scores for detecting PD-MCI and PDD were 9 and 7 points. The abbreviated version of the PDSFS includes the subscales of family life, hobbies, and self-care, with 27 points and a cut-off score of 25 points for PD-MCI. The comprehensive test comprises a simplified version of the MoCA and a simplified version of the PDSFS, with a total score of 43 points. We have simplified validation and simplified commonly used tests, and comprehensive tests can be helpful in the detection of PD-MCI and PDD.
簡短智能測驗(Mini-mental status examination)和蒙特利爾智能測驗(Montreal Cognitive Assessment)是臨床上常用於篩檢巴金森氏病患者（巴病）認知障礙的工具。我們發展了巴金森氏病社會功能量表(Parkinson's Disease Social Functioning Scale)且證實具良好的心理計量特性，可用於評估巴病患者的社會功能。本研究檢驗並簡化常用的臨床評估工具，發展兼顧認知與社會功能的綜合測驗。我們發現簡短智能測驗偵測巴病合併輕度認知障礙症的切截分數為26分，而蒙特利爾智能測驗偵測巴病合併輕度認知障礙症與巴病合併失智症的切截分數分別為23與18分。簡短版蒙特利爾智能測驗包含視覺空間/執行、記憶分測驗、定向感三個分測驗，滿分為16分，偵測巴病合併輕度認知障礙症與合併失智症的切截分數為9分與7分。簡版巴病社會功能量表包含家庭生活、嗜好與自理分量表，滿分為27分，巴病合併輕度認知障礙症的切截分數為25分。綜合測驗由簡版蒙特利爾智能測驗與簡版巴病社會功能量表組成，滿分為43分，偵測巴病合併輕度認知障礙症與合併失智症的切截分數為35分與30分。我們簡化了驗證並簡化了常用的測驗，且綜合測驗可助益於偵測巴病合併輕度認知障礙症與巴病合併失智症。
39. Adaptations of postural sway dynamics and cortical response to unstable stance with stroboscopic vision in older adults.
Tsai, Y.-Y., Chen, Y.-C., Zhao, C.-G., & Hwang, I.-S. (2022). Frontiers in Physiology, 13. Read this article
Background: Stroboscopic vision (SV), intermittent visual blocking, has recently been incorporated into postural training in rehabilitation. This study investigated interactions of postural fluctuation dynamics and cortical processing for the elderly during stabilometer stance with SV. Methods: Thirty-five healthy elderly maintained an upright stance on a stabilometer. Along with postural fluctuation dynamics, EEG relative power and EEG-EEG connectivity were used to contrast neuromechanical controls of stabilometer stance with SV and full-vision. Results: Compared with the full-vision, SV led to greater postural fluctuations with lower sample entropy and mean frequency (MF). SV also reduced regional power in the mid-frontal theta cluster, which was correlated to SV-dependent changes in the size of postural fluctuations. SV also enhanced the alpha band supra-threshold connectivity in the visual dorsal and frontal-occipital loops of the right hemisphere, and the supra-threshold connectivity from Fp2 positively related to variations in the MF of postural fluctuations. Conclusion: SV adds challenge to postural regulation on the stabilometer, with the increasing regularity of postural movements and fewer corrective attempts to achieve the postural goal. The elderly shift over-reliance on visual inputs for posture control with more non-visual awareness, considering deactivation of the dorsal visual stream and visual error processing.
40. Therapeutics for fulminant hepatitis caused by enteroviruses in neonates.
Wang, L.-C., Tsai, H.-P., Chen, S.-H., & Wang, S.-M. (2022). [Review]. Frontiers in Pharmacology, 13. 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.
41. Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant.
Hsiao, H.-T., Wang, J. C.-F., & Wu, S.-N. (2022). Biomedicines, 10(6), 1318. Read this article
Vortioxetine (VOR) is recognized to exert antidepressant actions. However, whether this drug modifies ionic currents in excitable cells remains unclear. The aim of this study was to explore the electrophysiological effects of VOR and other related compounds in pituitary GH3 cells and in Neuro-2a cells. VOR suppressed the delayed-rectifier K+ current (IK(DR)) in a concentration-, time-, and state-dependent manner. Effective IC50 values needed to inhibit peak and sustained IK(DR) were computed to be 31.2 and 8.5 μM, respectively, while the KD value estimated from minimal binding scheme was 7.9 μM. Cell exposure to serotonin (10 μM) alone failed to alter IK(DR), while fluoxetine (10 μM), a compound structurally similar to VOR, mildly suppressed current amplitude. VOR has been previously demonstrated to have an agonistic or antagonistic effect on HT receptors. Propranolol is an inhibitor of β-adrenergic and 5-HT receptors and risperidone can suppress dopamine receptors. In continued presence of VOR, neither further addition of propranolol nor risperidone reversed VOR-mediated inhibition of IK(DR). Increasing VOR concentration not only depressed IK(DR) conductance but also shifted toward the hyperpolarized potential. As the VOR concentration was raised, the recovery of IK(DR) block became slowed. The IK(DR) activated by a downsloping ramp was suppressed by its presence. The inhibition of IK(DR) by a train pulse was enhanced during exposure to VOR. In Neuro-2a cells, this drug decreased IK(DR). Overall, inhibitory effects of VOR on ionic currents might constitute another underlying mechanism of its actions.
A computational method, dubbed the simplified unit-cell micromechanics model, is generalized and applied to establish the effective nonlinear responses of three-phase magnetoelectric composites that are composed of two distinct magnetostrictive and piezoelectric phases embedded in elastic polymer matrices. To obtain effective nonlinear responses, a mathematical linearization is first introduced to perform the constitutive linearization for the nonlinear materials, and the resulting constitutive equations are then unified and nested into the micromechanics model followed by iterations in order to minimize errors from the linearization process. Numerical results are first validated against limited experimental measurements available in the literature. Parametric studies are then conducted in order to reveal the effect of phase constitutive laws, volume fractions, and geometries on the overall nonlinear responses of there-phase magnetoelectric composites. The contributions of this work complement those of earlier studies that prevalently devoted to two-phase magnetoelectric composites and linear magneto-electro-elastic coupled responses only.
Although YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive. Following manipulation of YAP1 or/and TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We found that YAP1 functions as a tumor suppressor whereas TAZ exerted pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression. We conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.
44. Pyrolysis of lignocellulosic, algal, plastic, and other biomass wastes for biofuel production and circular bioeconomy: A review of thermogravimetric analysis (TGA) approach.
Escalante, J., Chen, W.-H., Tabatabaei, M., Hoang, A. T., Kwon, E. E., Andrew Lin, K.-Y., & Saravanakumar, A. (2022). Renewable and Sustainable Energy Reviews, 169, 112914. Read this article
As a sustainable and renewable energy source, biomass has piqued interest in generating bioenergy and biofuels over recent years. Pyrolysis characteristics of different feedstock samples can be analyzed and examined through thermogravimetric analysis (TGA). TGA has been an essential tool and widely used to investigate the thermal characteristics of a substance under heating environments, such as thermodegradation dynamics and kinetics. Studying the potential of waste biomass for generating sustainable bioenergy carves a pathway into a circular bioeconomy regime, and can help tackle our heavy reliance on nonrenewable energy sources. This study aims to give a deep insight into the wide use of TGA in aiding in the research and development of pyrolysis of different waste biomass sources. The thermal characteristics portrayed by different biomass wastes through TGA are discussed. The effects of significant pyrolysis operating parameters are also illustrated. A more comprehensive understanding of evolved products during the pyrolysis stage can be gained by combining TGA with other analytical methods. Overall, an in-depth literature review helps identify current trends and technological improvements (i.e., integrating artificial intelligence) of TGA use with pyrolysis.
45. Postnatal Dexamethasone Therapy Impairs Brown Adipose Tissue Thermogenesis and Autophagy Flux in Neonatal Rat Pups.
Chang, Y. S., Hou, S. Y., Yu, S. S., Tsai, S. Y., Chen, Y. Y., Hsu, L. J., Tsai, P. J., Lin, H. K., Lin, C. H., & Tsai, Y. S. (2022). Theranostics, 12(13), 5803-5819. Read this article
Bronchopulmonary dysplasia (BPD) remains one of the greatest challenges in the field of neonatology. To date, systemic corticosteroids remain one of the few proven treatments for BPD. This study was to investigate the effects of postnatal short course Dex exposure on brown adipose tissue. We found that postnatal Dex treatment induced growth retardation, BAT whitening, UCP1 downregulation and cold intolerance in neonatal rats. BAT mitochondria were damaged, and autophagosome clearance was inhibited. AMPK activators could partially rescue thesedamages.
46. Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects.
Ko, P.-Y., Hsu, C.-C., Chen, S.-Y., Kuo, L.-C., Su, W.-R., Jou, I.-M., Su, F.-C., & Wu, P.-T. (2022). International Journal of Molecular Sciences, 23(17), 9760. Read this article
Although the combination of steroid and hyaluronic acid was thought to provide rapid pain relief and functional improvement in osteoarthritis, there is little evidence that these two combinations can treat tendinopathy. This study demonstrates that a specific ratio of steroid and hyaluronic acid formulation can improve tendinopathy through anti-apoptosis, anti-senescence and changing senescence-related secretory phenotypes without cytotoxicity. This study provides a possible approach to treat tendinopathy by using a specific combination of two known agents.
47. Cisplatin or Doxorubicin Reduces Cell Viability via the PTPIVA3-JAK2-STAT3 Cascade in Hepatocellular Carcinoma.
Li, C. J., Tsai, H. W., Chen, Y. L., Wang, C. I., Lin, Y. H., Chu, P. M., Chi, H. C., Huang, Y. C., & Chen, C. Y. (2023). J Hepatocell Carcinoma, 10, 123-138. Read this article
Hepatocellular carcinoma (HCC) accounts for 80% of all liver cancers and is the 2nd leading cause of cancer-related death in Taiwan. Various factors, including rapid cell growth, a high recurrence rate and drug resistance, make HCC difficult to cure. Moreover, the survival rate of advanced HCC patients treated with systemic chemotherapy remains unsatisfactory. Hence, the identification of novel molecular targets and the underlying mechanisms of chemoresistance in HCC and the development more effective therapeutic regimens are desperately needed. We found that protein tyrosine phosphatase IVA3 (PTP4A3) in the cisplatin/doxorubicin-resistant microarray was closely associated with the overall and recurrence-free survival rates of HCC patients. Furthermore, PTP4A3 was highly expressed in tumor tissues versus adjacent normal tissues from HCC patients. In addition, we evaluated the IL-6-associated signaling pathway involving STAT3 and JAK2, and the levels of p-STAT3, p-JAK2, STAT3 and JAK2 were obviously reduced with cisplatin or doxorubicin treatment in HCC cells. Collectively, we suggest that cisplatin or doxorubicin decreases HCC cell viability via downregulation of PTP4A3 expression through the IL-6R-JAK2-STAT3 cascade. Therefore, emerging evidence provides a deep understanding of the roles of PTP4A3 in HCC cisplatin/doxorubicin chemoresistance, which can be applied to develop early diagnosis strategies and reveal prognostic factors to establish novel targeted therapeutics to specifically treat HCC.
