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A face-to-face national survey in Taiwan was conducted to reflect the influence of animal welfare legislation on attitudes of the public (n = 1,099) towards animal welfare. Greater awareness and knowledge of the law correlated with a better attitude towards and preference for relevant animal protection issues in respondents. The lack of knowledge on animal welfare concepts, animal welfare products, and related labels among respondents appears to hinder the development of better animal welfare. Thus, promoting a better understanding of the law is fundamental and necessary. Improving animal welfare in Taiwan requires promotion of animal welfare concepts and markets in society not only through legislation, but also through education and implementation of better animal welfare policies.

Learner control of video presentations by using pause buttons or timeline scrollbars was suggested as helpful for learning from sources of transient information such as dynamic visualizations and spoken words. However, effective learner control could be difficult to attain without sufficient instructional support. This study developed strategies for facilitating processing and integration of transient information based on cognitive load theory by providing learners with explicit guidance in when and how to use pausing and timeline scrollbars while watching instructional videos. A single-factor between-subjects experiment was conducted to examine the effects of the proposed strategies. Ninety undergraduates were randomly assigned to one of three groups - strategy guidance group (learners were provided with guidance in strategies), learner control group (learners were allowed to control the video but without any guidance in strategies), and continuous presentation group (without any learner control mechanism). The results revealed that compared to the learner control group, the strategy guidance group had a greater number of pauses and scrollbacks on the timeline, demonstrated significantly better performance in the immediate comprehension test and higher performance efficiency in the immediate recall and comprehension tests. Compared to the continuous presentation group, the strategy guidance group demonstrated significantly better performance in the immediate recall and comprehension tests and higher performance efficiency in both these tests, as well as better performance in the delayed recall test and higher performance efficiency in the delayed recall test.

This study proposes a single-ended operational trans-conductance amplifier (SEOTA)-based triple inputs and single output high-input impedance voltage-mode (VM) universal second-order filter. The proposed universal VM SEOTA-based second-order filter can be realized for the non-inverting low-pass, non-inverting high-pass, non-inverting band-reject, non-inverting all-pass and inverting band-pass filtering functions by appropriately using different triple-input voltage signals. The high-input impedances of the proposed universal VM SEOTA-based configuration enable the second-order filter to be cascaded without additional buffers. The proposed configuration does not employ external resistors and accordingly is an active SEOTAs and capacitors (SEOTA-C) universal second-order filter. The proposed circuit using two grounded capacitors which is more apposite to further develop into an integrated circuit implementation. The resonance angular frequency and quality factor are orthogonal electronically adjustable. By slightly modifying the proposed universal VM SEOTA-based second-order filter configuration, the VM SEOTA-C quadrature sinusoidal oscillator is achieved. The oscillation frequency and the oscillation condition of the quadrature sinusoidal oscillator can be independently and electronically tuned by adjusting the bias currents of two SEOTAs. PSpice simulation results confirmed theoretic anticipation. The result of the experiment of the commercially available SEOTAs, LT1228s, are also used to verify the characteristics of the proposed universal VM SEOTA-based second-order filter and VM SEOTA-based quadrature sinusoidal oscillator.

Human mitochondrial NAD(P)+-dependent malic enzyme (ME2) is well-known for its role in cell metabolism, which may be involved in cancer or epilepsy. We present potent ME2 inhibitors based on cyro-EM structures that target ME2 enzyme activity. Two structures of ME2-inhibitor complexes demonstrate that 5,5’-Methylenedisalicylic acid (MDSA) and embonic acid (EA) bind allosterically to ME2’s fumarate-binding site. Mutagenesis studies demonstrate that Asn35 and the Gln64-Tyr562 network are required for both inhibitors’ binding. ME2 overexpression increases pyruvate and NADH production while decreasing the cell’s NAD+/NADH ratio; however, ME2 knockdown has the opposite effect. MDSA and EA inhibit pyruvate synthesis and thus increase the NAD+/NADH ratio, implying that these two inhibitors interfere with metabolic changes by inhibiting cellular ME2 activity. ME2 silence or inhibiting ME2 activity with MDSA or EA decreases cellular respiration and ATP synthesis. Our findings suggest that ME2 is crucial for mitochondrial pyruvate and energy metabolism, as well as cellular respiration, and that ME2 inhibitors could be useful in the treatment of cancer or other diseases that involve these processes.

Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD+/NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.

PURPOSE H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection. MATERIALS AND METHODS Patients with HBV, HCV, or dual HBV-HCV infection were enrolled from Taiwan's National Health Insurance Research Database and examined for the period from January 1, 2006, to December 31, 2015. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the association between AH use and HCC risk. RESULTS We included patients with HBV infection (n = 521,071), HCV (n = 169,159), and dual HBV-HCV (n = 39,016). Patients with HBV, HCV, or dual virus infection who used AHs exhibited significantly lower risk of HCC relative to patients who did not use AH, with their adjusted hazard ratio being 0.489 (95% CI, 0.455 to 0.524), 0.484 (95% CI, 0.450 to 0.522), and 0.469 (95% CI, 0.416 to 0.529), respectively. Furthermore, there was a dose-response relationship between AH use and the risk of HCC in the HBV cohort. The adjusted hazard ratios were 0.597 (95% CI, 0.530 to 0.674), 0.528 (0.465 to 0.600), 0.470 (0.416 to 0.531), and 0.407 (0.362 to 0.457) for AH use of 28-42, 43-63, 64-119, and ≥ 120 cumulative defined daily doses, respectively, relative to no AH use. Additionally, there was also a dose-response relationship between AH use and the risk of HCC in the HCV and dual HBV-HCV cohorts. CONCLUSION AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.

As the progress of science and technology and its application in medical treatment, the static computer-aided surgical guide for implant surgery is commonly used nowadays. For achieving a more accurate implant position, factors affecting the accuracy of the computer- aided surgical guide are generally concerned. The aim of this article was to perform a comprehensive overview of literatures and assessment of patient-related, guide stent-related and surgery-related factors affecting the accuracy of the static computer-aided implant surgical guide. It could be concluded that the position of guide, types of tissue support, fixation of guide, types of guided surgery (totally or partially guided), the sleeve length, the key height, and the distance between the sleeve and the implant platform might influence the accuracy of static computer-aided implant surgery. Knowledge of factors related to the accuracy of the surgical guide can aid the clinician to place implants precisely and safety, prevent complications and achieve predictable outcomes. &nbsp

We designed a robotic architecture system within a commercially available socially assistive robot to engage pairs of older adults in multimodal activities over 3 weeks for 6 sessions. The study took place in two assisted living facilities. Seven pairs (14 individuals) completed the experiment. Ages ranged from 70 to 90 years with a mean age of 83.0 (± 6.1). Most were women (79%). Three adults were screened as having normal cognition, 10 had mild cognitive impairment, and 1 adult self-reported a diagnosis of Alzheimer's disease. All sessions were video recorded and analyzed using Noldus Observer XT. Individuals demonstrated high levels of both human-human interaction and human-robot interaction, but the activity influenced the type of interaction. Engagement measures (visual, verbal, behavioral) also varied by type of activity. Future studies will focus on further development of activities that can engage older adults with varying levels of cognitive impairment and apathy.

Purpose No large-scale, prospective, randomized study has evaluated the effect of thoracic surgery on patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment. Therefore, we designed a propensity-score-matched, nationwide, population-based, cohort study to investigate the effects of thoracic surgery on patients with EGFR-mutant lung adenocarcinoma. Patients and Methods We included patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma and categorized them into two groups according to their treatment modalities and compared their outcomes: the case group consisted of patients who underwent thoracic surgery for lung tumors after receiving and responding to EGFR-TKI treatment and the comparison group consisted of patients who received EGFR-TKI treatment alone until tumor progression. Patients in both groups were matched at a ratio of 1:4. Results The matching process yielded a final cohort of 1395 patients (279 and 1,116 in the case and comparison groups, respectively) who were eligible for further analysis. According to multivariable Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) for thoracic surgery for lung tumors after EGFR-TKI use and tumor response (group 2) compared with EGFR-TKI treatment alone (group 1) was 0.445 (0.351–0.564). Conclusions Thoracic surgery prolonged overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKI treatment.

Background/Purpose Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. Methods The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. Results The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. Conclusion The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.

Current therapy does not provide significant benefits for patients with chronic stroke. Pre-clinical studies suggested that autologous adipose-derived stem cells have benefits for the treatment of chronic stroke. This Phase I open-label study was conducted to demonstrate the safety and efficacy of autologous adipose-derived stem cells (GXNPC1) in chronic stroke. Three patients with chronic stroke were treated with stereotactic implantation of autologous adipose-derived stem cells (1 × 108 cells). The primary endpoints of safety evaluation included adverse events, over a 6 months post-implantation period. The secondary endpoints included improvements in neurological functions. Evolutional change of brain parenchyma was also followed with magnetic resonance imaging (MRI). All three participants improved significantly at 6 months follow-up. The extent of improvement from pre-treatment was: National Institutes of Health Stroke Scale improved 5-15 points, Barthel Index: 25-50 points, Berg balance scale 0-21 points and Fugl-Meyer modified sensation 3-28 points. All three patients had signal change along the implantation tract on MRI one month after surgery. There is no related safety issue through 6 months observation. Clinical measures of neurological symptoms of these patients with chronic stroke improved at 6 months without adverse effects after implantation of autologous adipose-derived stem cells (GXNPC1), which might be correlated with post-implantation changes on brain MRI. Clinical Trial Registration-URL: https://clinicaltrials.gov/ct2/show/NCT02813512?term=ADSC&cond=Stroke&cntry=TW&draw=2&rank=1 Unique identifier: NCT02813512.

System pausing at pre-determined positions during multimedia presentations can enhance multimedia learning. However, the pause positions are usually set up based on the structure of the learning material (e.g., segmentation principle) rather than on the complexity of its different sections (as determined by levels of element interactivity, according to cognitive load theory). This study investigated the effectiveness of complexity-determined system pauses positioned either before or after complex (high element interactivity) sections of a slideshow multimedia presentation. The study adopted a single-factor between-subjects design and randomly assigned 128 undergraduates to four experimental conditions, namely (1) pausing before high element interactivity, (2) pausing after high element interactivity, (3) learner pausing and (4) no pausing. The research results revealed that complexity-determined system pausing approaches and learner pausing resulted in better test performance and instructional efficiency than the continuous presentation without pausing. The findings suggest that pauses allow students more time to deal with learning contents with high element interactivity, thus reducing potential cognitive overload and resulting in better performance compared with continuous presentation. However, no significant difference was found between the two types of system pausing and learner pausing in all measures.

Objectives RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. Methods This retrospective nationwide study used the 2000–2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. Results TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P 0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. Conclusions Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.

A high-sensitivity double-roughness-structure (DRS) and its innovative manufacturing processes are originally proposed for the improvement on the sensing of the non-reactive molecule. The nitrogen molecules are served as the non-reactive test target in the study. In the DRS, the high roughness graphene is embedded into/onto the roughness surface of the porous silicon, and such the porous silicon is specially made by the “bottom-hole assisted approach” to get high-quality films. It is proved that the DRS reveals the double reinforcement on the improvement of the sensitivity based on the high surface-to-volume ratio in the sensing on non-reactive molecules.

After ovulation, the mitochondrial enzyme CYP11A1 cleavage the cholesterol into pregnenolone for progesterone synthesis, suggesting that mitochondrial dynamics play a vital role in the female reproductive system. The changes in the mitochondria dynamics throughout the ovarian cycle have been reported in literature, but the correlation to its role in the ovarian cycle remains unclear. In this study, mitochondrial fusion promotor, M1, was used to study the impact of mitochondria dynamics in the female reproductive system. Our results showed that M1 treatment in mice can lead to the disruptions of estrous cycles in vagina smears. The decrease in serum LH was recorded in the animal. And the inhibitions of progesterone secretion and ovulations were observed in ovarian culture. Although no significant changes in mitochondrial networks were observed in the ovaries, significant up-regulation of mitochondrial respiratory complexes was revealed in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the molecules of extracellular matrix, remodeling enzymes, and adhesion signalings were decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive systems.

Contact engineering of two-dimensional semiconductors is a central issue for performance improvement of micro-/nanodevices based on these materials. Unfortunately, the various methods proposed to improve the Schottky barrier height normally require the use of high temperatures, chemical dopants, or complex processes. This work demonstrates that diffused electron beam energy (DEBE) treatment can simultaneously reduce the Schottky barrier height and enable the direct writing of electrical circuitry on van der Waals semiconductors. The electron beam energy projected into the region outside the electrode diffuses into the main channel, producing selective-area n-type doping in a layered MoTe

The aim of the present study was to investigate the variation of lower-limb kinematic characteristics and movement patterns in elite taekwondo competitors when performing roundhouse kicks at variou...

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially impacted human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2. Here, we demonstrated that acute SARS-CoV-2 infection elicits rapid and robust spike-binding and ACE2-blocking antibody responses, which wane approximately 11 months after infection. Serological responses were found to be correlated with the frequency of spike-specific memory B cell responses to natural infections. Further, significantly higher spike-binding, ACE2-blocking, and memory B cell responses were detected in patients with fever and pneumonia. Spike-specific antibody responses were found to be greatly affected by spike mutations in emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.ImportanceAs spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined the spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Further, the serological responses were correlated with the frequency of spike-specific memory B cell responses to natural infections. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. Moreover, the spike-specific antibody responses were substantially affected by the emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

Redundancy effect has been investigated in many controlled experimental studies, however, it is seldom investigated whether the same redundant material may cause different results in classroom, which is a major learning place for students. Considering that it is not easy to control the internal validity in classroom environment, this study proposed a new research approach with the use of virtual reality (VR) classroom as the experimental platform to investigate this issue. In the current study, one hundred and four fifth-grade students were randomly assigned to four experimental conditions with two different presentation formats (redundant and non-redundant) and two learning environments (lab and VR classroom). The retention test scores, cognitive load, and performance efficiency were used as dependent variables. The results revealed that the redundancy effect occurred in the lab environment and the reverse redundancy effect occurred in the VR classroom environment. In the lab environment, participants who had learned with non-redundant materials demonstrated better learning performance than those who had learned with redundant materials. On the contrary, the results were reversed in the VR classroom environment. The programmed interferences in the VR classroom are suggested as the main factor influencing the results.

BACKGROUND Transgender individuals often require gender-affirming interventions, such as endogenous sex hormone inhibition or gender-affirming hormone therapy (HT), while there is discordance between their body and gender identity. However, a recent study found that the incidence of cardiovascular events is higher in transgender patients receiving cross-sex HT. The aim of this study was to investigate the metabolic effects of an altered sex hormone profile. METHODS This retrospective study, conducted in a referral center in Northern Taiwan, analyzed metabolic changes over time in 65 trans masculine and 45 trans feminine persons. The transgender individuals were examined at 4 time points: before the gender affirming HT, as well as 3, 6, and 12 months following treatment. RESULTS Compared with baseline measurements, the trans masculine patients showed significant increases in body mass index (BMI) (22.6 ± 0.3 vs 23.3 ± 0.4 kg/m2; p < 0.001; t = 3M), low-density lipoprotein cholesterol (124.3 ± 3.7 vs 131.3 ± 3.9 mg/dL; p = 0.03; t = 12M), creatinine (0.75 ± 0.01 vs 0.83 ± 0.14 mg/dL; p < 0.001; t = 12M), and hemoglobin (13.5 ± 0.7 vs 15.2 ± 0.2 g/dL; p < 0.001; t = 12M), as well as decreased high-density lipoprotein cholesterol (57 ± 2.1 vs 51 ± 2.0 mg/dL; p < 0.001; t = 12M). The trans feminine patients had reduced low-density lipoprotein cholesterol (104.2 ± 3.2 vs 100.8 ± 3.5 mg/dL; p = 0.05; t = 3M), hemoglobin (14.0 ± 0.1 vs 13.5 ± 0.1 g/dL; p = 0.008; t = 12M), and creatinine (0.82 ± 0.01 vs 0.79 ± 0.14 mg/dL; p < 0.001; t = 3M) compared with baseline data. In addition, most of these metabolic effects persisted during the follow-up period. CONCLUSION This observational, retrospective study revealed that gender-affirming HT increased the relative cardiovascular risk in trans masculine individuals.

Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.

S Our previous study first investigated feasibility of applying ultrasound (US) and microbubbles (MBs) via external auditory canal to facilitate drug delivery into inner ear. However, most drugs are in aqueous formulae and eliminated via Eustachian tubes after drug application. In this study, feasibility of sustained release of thermosensitive poloxamer 407 (P407)-based MB gel for US mediation-enhanced inner ear drug (dexamethasone, DEX) delivery was investigated. The sol-to-gel transition temperature showed that mixture of DEX and only 10% and 12.5% P407 in MBs can be used for in vitro and in vivo drug delivery experiments. In in vitro Franz diffusion experiments, the release rates of 12.5% P407-MBs + US groups in the model using DEX as the delivered reagent at 3 h resulted in values 1.52 times greater than those of 12.5% P407-MBs groups. In guinea pigs, by filling tympanic bulla with DEX in 12.5% P407-MBs (DEX-P407-MBs), USMB applied at post-treatment days 1 and 7 induced 109.13% and 66.67% increases in DEX delivery efficiencies, respectively, compared to the group without US. On the 28th day after US-mediated P407-MB treatment, the safety assessment showed no significant changes in the hearing thresholds and no damage to the integrity of cochlea or middle ear. These are the first results to demonstrate feasibility of US-modified liquid form DEX-P407-MB cavitation for enhancing permeability of round window membrane. Then, a gel form of DEX-P407-MBs was generated and thus prolonged the release of DEX in middle ear to maintain the therapeutic DEX level in inner ear for at least 7 days.

Using a self‐administered questionnaire (the five‐item Brief Symptom Rating Scale, BSRS‐5), determine the prevalence of suicide ideation (SI), psychiatric morbidity (PM), and the factors associated with these conditions in a general hospital in Taiwan. All individuals aged 12 years or older, who were admitted to a Medical University Hospital between August 2014 and December 2016, were asked to fill out the BSRS‐5 at admission. The study was conducted in a medical inpatient setting, excluding Intensive Care Units and the Emergency Service Department. The 93,129 participants were recruited for analysis. Pearson's correlation, regression analysis and path analysis were performed to test the association between SI and each item of psychopathology and to determine the discrimination validity of individual BSRS‐5 items for predicting SI. The prevalence rate was 2.3% for SI and 2.0% for PM among all participants. PM was more prevalent in females and those aged 25–54 years. Individuals with PM had a significantly higher rate of SI (44.6%) than did others (1.4%). The prevalence of PM was varied by department, e.g., Psychiatry (44.3%), Rehabilitation Medicine (7.9%), and Nephrology (5.2%). The regression analysis and path analysis with structural equation model indicated that depression, hostility, anxiety, and inferiority were significant independent predictors of SI. The BSRS‐5 is an efficient and useful screening tool to identify psychological distress and SI among inpatients in a general hospital. Its integration into the electronic medical chart facilitates identifying patients at risk.

Lane width evaluation is one of the crucial aspects in road safety inspection, especially in work zones where a narrow lane width can result in a reduced roadway capacity and also, increase the probability of severe accidents. Using mobile mapping systems (MMS) equipped with laser scanners is a safe and cost-effective method for rapidly collecting detailed information along road surface. This paper presents an approach to derive lane width estimates using point clouds acquired from a geometrically-calibrated mobile mapping system. Starting from an accurate LiDAR point cloud, the road surface is extracted with the assistance of trajectory elevation data. Lane markings are identified based on the intensity data. Next, the lane marking centerline is derived and clustered to identify areas with ambiguous or missing lane markings and finally, use the normal (or, unambiguous) lane markings to estimate the lane width. The derived lane width estimates are used to develop a reporting mechanism for areas with narrow lanes, ambiguous lane markings, missing lane markings, and/or wide lanes.

PurposeCareer plateau is a major concern for many seasoned employees because they often stay in the same position longer than expected and over time begin to lack job challenges. This phenomenon is now considered a normal stage in career development. The purpose of this study is to test the effects of two types of career plateau: hierarchical and job content on career commitment (career identity, career insight and career resilience), along with the mediating effect of perceived external employability. We also determined in the moderated mediation model if Super's (1957) three career stages amplify and attenuate the indirect effect of hierarchical/job content plateau on career commitment (career identity, career insight, career resilience) via perceived external employability.Design/methodology/approachWe tested the hypotheses with survey data collected from a convenience sample of 472 white-collar full-time employees who also studied in the MBA and continuing education program in five large universities in Taiwan (77% return rate).FindingsThe mediation model result showed that perceived external employability partially and negatively mediated the influence of hierarchical plateaus on career commitment (career identity, career insight and career resilience). Perceived external employability partially and negatively mediated the influence of job content plateaus on career identity and career insight but fully and negatively mediated on career resilience. The result of the moderated mediation model also demonstrated that only employees in the trial stage had influences on the mediation relationships among the hierarchical plateau, perceived external employability and career commitment with its two dimensions of career identity and career insight only other than those in the stabilization and maintenance stages.Practical implicationsThe findings of this study can benefit career management scholars and practitioners since they promote a better understanding of the career management practices that are relevant for seasoned employees who are valued for their knowledge, experience and expertise when encountering the three career stages.Originality/valueDrawing on the conservation of resources (COR) theoretical perspective, we fill the gap in the literature by proposing perceived external employability as a mediator in the link between career plateau and career commitment and generalize the results to plateaued employees at the different career stages.

Ketamine-associated cystitis is characterized by suburothelial inflammation and urothelial cell death. Norketamine (NK), the main metabolite of ketamine, is abundant in urine following ketamine exposure. NK has been speculated to exert toxic effects in urothelial cells, similarly to ketamine. However, the molecular mechanisms contributing to NK-induced urothelial cytotoxicity are almost unclear. Here, we aimed to investigate the toxic effects of NK and the potential mechanisms underlying NK-induced urothelial cell injury. In this study, NK exposure significantly reduced cell viability and induced apoptosis in human urinary bladder epithelial-derived RT4 cells that NK (0.01-0.5 mM) exhibited greater cytotoxicity than ketamine (0.1-3 mM). Signals of mitochondrial dysfunction, including mitochondrial membrane potential (MMP) loss and cytosolic cytochrome c release, were found to be involved in NK-induced cell apoptosis and death. NK exposure of cells also triggered the expression of endoplasmic reticulum (ER) stress-related proteins including GRP78, CHOP, XBP-1, ATF-4 and -6, caspase-12, PERK, eIF-2α, and IRE-1. Pretreatment with 4-phenylbutyric acid (an ER stress inhibitor) markedly prevented the expression of ER stress-related proteins and apoptotic events in NK-exposed cells. Additionally, NK exposure significantly activated JNK, ERK1/2, and p38 signaling and increased intracellular calcium concentrations ([Ca

Rapid development and deployment of vaccines is crucial to control the continuously evolving COVID-19 pandemic. The placebo-controlled phase 3 efficacy trial is still the standard for authorizing vaccines in the majority of the world. However, due to a lack of eligible participants in parts of the world, this has not always been feasible. Recently, the Taiwan Food and Drug Administration, following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Here, we describe a study in which our candidate vaccine, MVC-COV1901, an adjuvanted protein subunit vaccine, has been granted emergency use authorization (EUA) in Taiwan based on a noninferiority immunobridging study. Immunogenicity results from the per protocol immunogenicity (PPI) subset (n = 903) from the MVC-COV1901 phase 2 trial were compared with results from 200 subjects who had received an adenovirus vector vaccine, AstraZeneca ChAdOx nCOV-19 (AZD1222), in a separate study. The lower bound of the 95% confidence interval (CI) of the geometric mean titer (GMT) ratio comparing MVC-COV1901 to AZD1222 was 3.4. The lower bound of the 95% CI of the sero-response rate was 95.5%. Both the GMT ratio and sero-response rate exceeded the criteria established by the Taiwan regulatory authority, leading to EUA approval of MVC-COV1901 in Taiwan.

BackgroundRapid development and deployment of vaccine is crucial to control the continuously evolving COVID-19 pandemic. Placebo-controlled phase 3 efficacy trial is still standard for authorizing vaccines in majority of the world. However, due to lack of cases or participants in parts of the world, this has not always been feasible. An alternative to efficacy trial is immunobridging, in which the immune response or correlates of protection of a vaccine candidate is compared against an approved vaccine. Here we describe a case study where our candidate vaccine, MVC-COV1901, has been granted for emergency use authorization (EUA) locally based on the non-inferiority immunobridging process.MethodsThe per protocol immunogenicity (PPI) subset from the MVC-COV1901 phase 2 trial was used for this study and consisted of 903 subjects who have received two doses of MVC-COV1901 as scheduled in the clinical trial. The comparator set of population consisted of 200 subjects of ≥ 20 years of age who were generally healthy and have received two doses of AstraZeneca ChAdOx nCOV-19 (AZD1222) recruited from Taoyuan General Hospital, Ministry of Health and Welfare.ResultsMVC-COV1901 was shown to have a geometric mean titer (GMT) ratio lower bound 95% confidence interval (CI) of 3.4 against the comparator vaccine and a seroconversion rate of 95.5% at the 95% CI lower bound, which both exceeded the criteria set by the Taiwan regulatory authority for EUA approval. These results supported the EUA approval of MVC-COV1901 by the Taiwanese regulatory authority in July 2021. Following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), countries from the Access Consortium has recently adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data.ConclusionThe data presented in the study showed that it is reasonably likely that the vaccine efficacy of MVC-COV1901 is similar or superior to that of AZ. Data could be used in support of further vaccine development and regulatory approval.

IntroductionEndovascular therapies are the first-line treatment for splanchnic aneurysms. However, after failed endovascular therapies or giant aneurysms with mass effects, appropriate management for splanchnic aneurysms remained inconclusive.MethodA retrospective review was performed for consecutive patients (from 2019 to 2021) who underwent salvage surgeries following failed endovascular therapies for splanchnic artery aneurysms. Salvage operations included total aneurysmectomy with end-to-end vascular reconstruction and partial aneurysmectomy with directly closing bleeders from the intraluminal space of the aneurysms.ResultFour patients received salvage surgeries for three false aneurysms of the celiac or superior mesenteric arteries and a true aneurysm of the common hepatic artery. The causes of failed endovascular therapies included coil migration, insufficient space for safely deploying the endovascular stent or persistent mass effect from the thrombosed giant aneurysm. Mean hospital stay was five days (range, 3-7 days), with 0% of morbidity and mortality rate and 100% of symptoms improvement. During the follow-up period (mean, 8.75 months; range, 4-15 months), one patient suffered a small residual asymptomatic celiac artery aneurysm (8 mm in diameter) and was treated conservatively due to underlying liver cirrhosis.ConclusionSurgical management is a feasible, effective, and safe alternative for splanchnic aneurysms undergoing failed endovascular therapies.

Acromegaly is associated with cardiovascular alterations. Up to 50% acromegalic patients suffered from treatment failure after multiple modalities. We investigated correlation between cardiovascular function and control of growth hormone (GH) in acromegalic patients following transsphenoidal adenomectomy (TSA).We recruited acromegalic patients who had undergone TSA between 2006 and 2014 in this cross-sectional study. Patients were assigned to group 1, controlled acromegaly (GH1.0 ng/mL and normalized insulin-like growth factor-1 [IGF-1]); group 2, partially controlled acromegaly (either GH1.0 ng/mL or non-normalized IGF-1); or group 3, uncontrolled acromegaly (GH1.0 ng/mL and non-normalized IGF-1). Echocardiography evaluated the left ventricular mass index, left ventricular ejection fraction, and the early transmitral filling velocity (E)-to-late transmitral filling velocity (A) and the E-to-the early diastolic mitral annular velocity (E') ratios. Carotid tonometry evaluated the intima-media thickness of the carotid artery, carotid-femoral pulse wave velocity, augmentation index, aortic characteristic impedance (Zc), and pulse pressure amplification.Thirty-three patients participated in this study. Fourteen of the 33 patients were males (42%). Mean age at diagnosis was 50.33 years (SD 18.45). Compared to patients in group 1, patients in group 3 had younger age and shorter years after operation, without statistical significance. Cumulative GH levels were progressively higher from group 1 to group 3, without statistical significance. The groups did not differ with respect to cardiovascular structure and function evaluated by echocardiography and carotid tonometry. Only Zc value had a difference that was of borderline significance (group 1: 109.13 ± 32.99; group 2: 129.30 ± 32.27; group 3: 159.56 ± 77.4 dynes × s/cm5; ANOVA p = 0.088; p = 0.086 for group 1 vs group 3).In the patients with acromegaly who had undergone TSA, cardiac structure and vascular stiffness did not differ among the groups with different levels of GH control.

Flexible manipulation of the carrier transport behaviors in two-dimensional materials determines their values of practical application in logic circuits. Here, we demonstrated the carrier-type mani...

Roadside ditches serve an important role for draining storm water. Over time vegetation growth, natural sediment deposits, and other debris can change grade of ditches. Effectively monitoring and identifying these changes to prioritize ditch maintenance is important from both a pavement preservation perspective and prevention of localized flooding. This study evaluates the performance of two mobile LiDAR systems for mapping the cross-section of roadside ditches in the presence of vegetation. The geometric quality of data collected by two different wheel-based LiDAR systems were investigated. The mapped ditches were reported and visualized in 2D images as well as 3D point clouds. The cross-sections of man-made drainage ditches were extracted and the quality of mapped ditches was assessed against Real-Time Kinematic Global Navigation Satellite Systems (RTK-GNSS) survey. The overall point cloud accuracy was 4 cm for the medium-grade system, and 1 cm for the high-grade system. The mapping accuracy is 2 cm (medium-grade system) and 1 cm (high-grade system) for solid surface. For rough mowed areas and areas with significant vegetation, the vertical accuracy was found to be 7 cm and 11 cm, respectively, for both wheel-based systems.

By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients' blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.

Although a modality effect indicating better learning from an animation with spoken learning guidance than from an animation with written learning guidance has often been found in research on learning from animation, the effect has hardly been investigated for learning from computer simulation. This study examined the interaction effects between the multimedia types of animation and computer simulation, and the presentation modes of written and spoken learning guidance. Based on cognitive load theory and the specific characteristics of the multimedia types it was hypothesized that a modality effect would be replicated in the animation condition and a reverse modality effect would be found in the simulation condition. Results partially supported the hypotheses, indicating that participants learned more from animation when it was accompanied with spoken text, and from a simulation when it was accompanied with written text. However, no effect was found for cognitive load. Based on the results, spoken text is recommended to be used to guide learners in animations assisted learning environments, and written text is recommended to be used to guide learners in simulations assisted learning environments. Practitioner Notes What is already known about this topic Animation and computer simulation have been widely used in different learning fields. Modality effect means that students learn more from graphical representations when they are accompanied with spoken text instead of written text. The modality effect has been verified in different learning environments. What this paper adds Examined the interaction effects between the multimedia types of animation and computer simulation, and the presentation modes of written and spoken text in a learning guide. Provided recommendations for designing the leaning guide of animation and simulation based on cognitive load theory. Implications for practice and/or policy Modality effect was verified in animation, and thus, spoken text is more suitable for learning from animation. Reversed modality effect was found in simulation condition, and thus, written text is more suitable for learning from simulation.

Objectives The data concerning the association between Tx and ADs remain unclear and are scarce. This study was undertaken to investigate whether people with Tx are more likely to develop ADs, compared to those without Tx. Methods Individuals who received Tx between 2002 and 2015 were identified and matched on age and sex with individuals without Tx. We performed multivariate and stratified analysis using the Kaplan–Meier method and Cox proportional hazards models in order to estimate the association between Tx and the risk of developing ADs. Results A total of 2550 thymectomized (Txd) patients and 24,664.941 non‐Txd comparison subjects were selected from NHIRD. Tx‐MG (myasthenia gravis) as compared with general population (nonTx‐nonMG), adjusted hazard ratio (aHR) were higher for incident Addison disease (aHR = 10.40, 95% CI 1.01–107), autoimmune hemolytic anemia (aHR = 21.54, 95% CI 2.06–14.8), Hashmoto thyroiditis (aHR = 5.52, 95% CI 1.34–34.7), ankylosing spondylitis (aHR = 2.73, 95% CI 1.09–6.84), rheumatoid arthritis (aHR = 5.25, 95% CI 1.79–15.47), primary Sjogren syndrome (pSS) (aHR = 3.77, 95% CI 1.30–11.0), and systemic lupus erythemtoasus (aHR = 10.40). Tx‐nonMG as compared with general population, aHR were higher for incident autoimmune hemolytic anemia (aHR = 25.50), Hashmoto thyroiditis (aHR = 6.75) and systemic lupus erythematosus (SLE) (aHR = 13.38). NonTx‐MG as compared with general population, aHR were higher for incident Hashmoto thyroiditis (aHR = 6.57), pSS (aHR = 4.50), SLE (aHR = 17.29), and systemic vasculitis (aHR = 25.86). Interpretation In conclusion, based on a retrospective cohort study throughout Taiwan, patients with Tx have a higher risk of new onset ADs than patients without Tx.